dbSNP rs76597070: CCDC27:p.Arg104Lys (chr1-3752792-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_152492.3(CCDC27):c.311G>A(p.Arg104Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00949 in 1,611,598 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0063 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0098 ( 78 hom. )

Consequence

CCDC27
NM_152492.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.145

Publications

11 publications found

Variant links:

Genes affected

CCDC27 (HGNC:26546): (coiled-coil domain containing 27)

CCDC27 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003395021).

BP6

Variant 1-3752792-G-A is Benign according to our data. Variant chr1-3752792-G-A is described in ClinVar as Benign. ClinVar VariationId is 788937.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152492.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC27	NM_152492.3	MANE Select	c.311G>A	p.Arg104Lys	missense	Exon 1 of 12	NP_689705.2	Q2M243

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC27	ENST00000294600.7	TSL:1 MANE Select	c.311G>A	p.Arg104Lys	missense	Exon 1 of 12	ENSP00000294600.2	Q2M243
CCDC27	ENST00000462521.2	TSL:5	n.311G>A		non_coding_transcript_exon	Exon 1 of 12	ENSP00000463275.1	J3QKX2
CCDC27	ENST00000636250.1	TSL:5	n.821G>A		non_coding_transcript_exon	Exon 4 of 6

Frequencies

GnomAD3 genomes

AF:

0.00636

AC:

968

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0111

Gnomad OTH

AF:

0.00766

GnomAD2 exomes

AF:

0.00636

AC:

1582

AN:

248854

AF XY:

0.00677

show subpopulations

Gnomad AFR exome

AF:

0.00126

Gnomad AMR exome

AF:

0.00279

Gnomad ASJ exome

AF:

0.00210

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00354

Gnomad NFE exome

AF:

0.0109

Gnomad OTH exome

AF:

0.00727

GnomAD4 exome

AF:

0.00982

AC:

14326

AN:

1459252

Hom.:

Cov.:

AF XY:

0.00966

AC XY:

7009

AN XY:

725532

show subpopulations

African (AFR)

AF:

0.00120

AC:

AN:

33454

American (AMR)

AF:

0.00327

AC:

146

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.00184

AC:

AN:

26100

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39634

South Asian (SAS)

AF:

0.00387

AC:

334

AN:

86210

European-Finnish (FIN)

AF:

0.00412

AC:

217

AN:

52716

Middle Eastern (MID)

AF:

0.00261

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0118

AC:

13077

AN:

1110412

Other (OTH)

AF:

0.00743

AC:

448

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

800

1600

2401

3201

4001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

482

964

1446

1928

2410

<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:

0.00635

AC:

967

AN:

152346

Hom.:

Cov.:

AF XY:

0.00599

AC XY:

446

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00168

AC:

AN:

41596

American (AMR)

AF:

0.00503

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00228

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00311

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0111

AC:

754

AN:

68022

Other (OTH)

AF:

0.00758

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

144

192

240

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:

0.00900

Hom.:

Bravo

AF:

0.00672

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.0114

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0102

AC:

ExAC

AF:

0.00677

AC:

822

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0103

EpiControl

AF:

0.00914

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.6

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.0051

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.29

MetaRNN

Benign

0.0034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.63

PhyloP100

-0.14

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.46

REVEL

Benign

0.018

Sift

Benign

0.38

Sift4G

Benign

0.42

Polyphen

0.0070

Vest4

0.076

MVP

0.072

MPC

0.35

ClinPred

0.0013

GERP RS

-0.27

PromoterAI

0.055

Neutral

(source)

Varity_R

0.042

gMVP

0.053

Mutation Taster

=100/0

polymorphism

(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

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