Genetic Variant CFAP20DC:p.Arg222His (chr3-58884595-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001394063.1(CFAP20DC):c.665G>A(p.Arg222His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,613,784 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 10 hom., cov: 32)

Exomes 𝑓: 0.011 ( 121 hom. )

Consequence

CFAP20DC
NM_001394063.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.678

Publications

9 publications found

Variant links:

Genes affected

CFAP20DC (HGNC:24763): (CFAP20 domain containing)

CFAP20DC links:

CFAP20DC-AS1 (HGNC:41063): (CFAP20DC antisense RNA 1)

CFAP20DC-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007875681).

BP6

Variant 3-58884595-C-T is Benign according to our data. Variant chr3-58884595-C-T is described in ClinVar as Benign. ClinVar VariationId is 774300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 10 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394063.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CFAP20DC	NM_001394063.1	MANE Select	c.665G>A	p.Arg222His	missense	Exon 7 of 17	NP_001380992.1	A0A2U3TZK7
CFAP20DC	NM_001351531.2		c.50G>A	p.Arg17His	missense	Exon 6 of 16	NP_001338460.1
CFAP20DC	NM_198463.4		c.290G>A	p.Arg97His	missense	Exon 7 of 16	NP_940865.1	Q6ZVT6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CFAP20DC	ENST00000482387.7	TSL:5 MANE Select	c.665G>A	p.Arg222His	missense	Exon 7 of 17	ENSP00000417122.2	A0A2U3TZK7
CFAP20DC	ENST00000468415.6	TSL:1	n.*84G>A		non_coding_transcript_exon	Exon 7 of 15	ENSP00000419142.2	F8WF72
CFAP20DC	ENST00000468415.6	TSL:1	n.*84G>A		3_prime_UTR	Exon 7 of 15	ENSP00000419142.2	F8WF72

Frequencies

GnomAD3 genomes

AF:

0.00727

AC:

1105

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00727

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0106

Gnomad FIN

AF:

0.00633

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0117

Gnomad OTH

AF:

0.00525

GnomAD2 exomes

AF:

0.00739

AC:

1859

AN:

251390

AF XY:

0.00809

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00243

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00795

Gnomad NFE exome

AF:

0.0108

Gnomad OTH exome

AF:

0.00619

GnomAD4 exome

AF:

0.0113

AC:

16508

AN:

1461630

Hom.:

121

Cov.:

AF XY:

0.0114

AC XY:

8260

AN XY:

727126

show subpopulations

African (AFR)

AF:

0.00149

AC:

AN:

33470

American (AMR)

AF:

0.00244

AC:

109

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00138

AC:

AN:

26128

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39686

South Asian (SAS)

AF:

0.0118

AC:

1019

AN:

86248

European-Finnish (FIN)

AF:

0.00889

AC:

475

AN:

53416

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0128

AC:

14283

AN:

1111804

Other (OTH)

AF:

0.00871

AC:

526

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

861

1722

2582

3443

4304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.00726

AC:

1104

AN:

152154

Hom.:

Cov.:

AF XY:

0.00706

AC XY:

525

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.00161

AC:

AN:

41508

American (AMR)

AF:

0.00727

AC:

111

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.0104

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00633

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0117

AC:

794

AN:

67998

Other (OTH)

AF:

0.00520

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

120

179

239

299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00962

Hom.:

Bravo

AF:

0.00665

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0108

AC:

ExAC

AF:

0.00739

AC:

897

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0104

EpiControl

AF:

0.00925

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0079

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

0.68

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.65

REVEL

Benign

0.0050

Sift

Benign

0.26

Sift4G

Benign

0.36

Polyphen

0.045

Vest4

0.22

MVP

0.28

MPC

0.19

ClinPred

0.0059

GERP RS

1.8

gMVP

0.36

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over