rs78910014

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_144668.6(CFAP251):c.1250G>A(p.Arg417Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0446 in 1,582,920 control chromosomes in the GnomAD database, including 1,898 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 142 hom., cov: 32)

Exomes 𝑓: 0.045 ( 1756 hom. )

Consequence

CFAP251
NM_144668.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.651

Publications

12 publications found

Variant links:

Genes affected

CFAP251 (HGNC:28506): (cilia and flagella associated protein 251) This protein encoded by this gene belongs to the WD repeat-containing family of proteins, which function in the formation of protein-protein complexes in a variety of biological pathways. This family member appears to function in the determination of mean platelet volume (MPV), and polymorphisms in this gene have been associated with variance in MPV. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2011]

CFAP251 Gene-Disease associations (from GenCC):

spermatogenic failure 33
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
non-syndromic male infertility due to sperm motility disorder
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CFAP251 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012010038).

BP6

Variant 12-121949042-G-A is Benign according to our data. Variant chr12-121949042-G-A is described in ClinVar as [Benign]. Clinvar id is 403607.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0373 (5674/152054) while in subpopulation SAS AF = 0.0544 (262/4812). AF 95% confidence interval is 0.049. There are 142 homozygotes in GnomAd4. There are 2706 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 142 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP251	NM_144668.6 link	c.1250G>A	p.Arg417Gln	missense_variant	Exon 8 of 22	ENST00000288912.9	NP_653269.3	Q8TBY9-1
CFAP251	NM_001178003.2 link	c.1250G>A	p.Arg417Gln	missense_variant	Exon 8 of 18		NP_001171474.1	Q8TBY9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CFAP251	ENST00000288912.9 link	c.1250G>A	p.Arg417Gln	missense_variant	Exon 8 of 22	1	NM_144668.6	ENSP00000288912.4	Q8TBY9-1
CFAP251	ENST00000397454.2 link	c.1250G>A	p.Arg417Gln	missense_variant	Exon 8 of 18	1		ENSP00000380595.2	Q8TBY9-2
CFAP251	ENST00000543211.5 link	n.1374G>A		non_coding_transcript_exon_variant	Exon 1 of 5	3
CFAP251	ENST00000546044.1 link	n.359G>A		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.0373

AC:

5663

AN:

151936

Hom.:

140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0124

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0412

Gnomad ASJ

AF:

0.0923

Gnomad EAS

AF:

0.0372

Gnomad SAS

AF:

0.0542

Gnomad FIN

AF:

0.0258

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0495

Gnomad OTH

AF:

0.0451

GnomAD2 exomes

AF:

0.0400

AC:

9313

AN:

232652

AF XY:

0.0416

show subpopulations

Gnomad AFR exome

AF:

0.0116

Gnomad AMR exome

AF:

0.0241

Gnomad ASJ exome

AF:

0.0827

Gnomad EAS exome

AF:

0.0282

Gnomad FIN exome

AF:

0.0267

Gnomad NFE exome

AF:

0.0465

Gnomad OTH exome

AF:

0.0435

GnomAD4 exome

AF:

0.0454

AC:

64983

AN:

1430866

Hom.:

1756

Cov.:

AF XY:

0.0456

AC XY:

32482

AN XY:

711748

show subpopulations

African (AFR)

AF:

0.0110

AC:

353

AN:

32210

American (AMR)

AF:

0.0264

AC:

1084

AN:

41072

Ashkenazi Jewish (ASJ)

AF:

0.0825

AC:

2108

AN:

25548

East Asian (EAS)

AF:

0.0439

AC:

1681

AN:

38274

South Asian (SAS)

AF:

0.0486

AC:

3919

AN:

80682

European-Finnish (FIN)

AF:

0.0268

AC:

1417

AN:

52920

Middle Eastern (MID)

AF:

0.0480

AC:

273

AN:

5684

European-Non Finnish (NFE)

AF:

0.0470

AC:

51440

AN:

1095412

Other (OTH)

AF:

0.0458

AC:

2708

AN:

59064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.427

Heterozygous variant carriers

2670

5341

8011

10682

13352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1980

3960

5940

7920

9900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0373

AC:

5674

AN:

152054

Hom.:

142

Cov.:

AF XY:

0.0364

AC XY:

2706

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.0124

AC:

516

AN:

41516

American (AMR)

AF:

0.0410

AC:

626

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.0923

AC:

320

AN:

3468

East Asian (EAS)

AF:

0.0371

AC:

192

AN:

5180

South Asian (SAS)

AF:

0.0544

AC:

262

AN:

4812

European-Finnish (FIN)

AF:

0.0258

AC:

271

AN:

10524

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0495

AC:

3366

AN:

67984

Other (OTH)

AF:

0.0498

AC:

105

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

270

541

811

1082

1352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0456

Hom.:

390

Bravo

AF:

0.0356

TwinsUK

AF:

0.0502

AC:

186

ALSPAC

AF:

0.0501

AC:

193

ESP6500AA

AF:

0.0119

AC:

ESP6500EA

AF:

0.0446

AC:

361

ExAC

AF:

0.0425

AC:

5135

Asia WGS

AF:

0.0670

AC:

234

AN:

3454

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.84

CADD

Benign

8.4

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.0039

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.50

T;T

MetaRNN

Benign

0.0012

T;T

MetaSVM

Benign

-0.92

PhyloP100

0.65

PrimateAI

Benign

0.24

PROVEAN

Benign

2.4

N;N

REVEL

Benign

0.043

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.049

MPC

0.15

ClinPred

0.00050

GERP RS

-0.91

Varity_R

0.030

gMVP

0.20

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over