dbSNP rs1334687036: C2CD4D:p.Pro154Gln (chr1-151838529-G-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_001394591.1(C2CD4D):c.461C>A(p.Pro154Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000128 in 1,345,236 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 2 hom. )

Consequence

C2CD4D
NM_001394591.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.48

Publications

2 publications found

Variant links:

Genes affected

C2CD4D (HGNC:37210): (C2 calcium dependent domain containing 4D)

C2CD4D links:

C2CD4D-AS1 (HGNC:54045): (C2CD4D and THEM5 antisense RNA 1)

C2CD4D-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3302924).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394591.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C2CD4D	NM_001394591.1	MANE Select	c.461C>A	p.Pro154Gln	missense	Exon 2 of 2	NP_001381520.1	B7Z1M9
C2CD4D	NM_001136003.2		c.461C>A	p.Pro154Gln	missense	Exon 2 of 2	NP_001129475.1	B7Z1M9
C2CD4D	NM_001394592.1		c.461C>A	p.Pro154Gln	missense	Exon 2 of 2	NP_001381521.1	B7Z1M9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C2CD4D	ENST00000694868.1	MANE Select	c.461C>A	p.Pro154Gln	missense	Exon 2 of 2	ENSP00000511551.1	B7Z1M9
C2CD4D	ENST00000454109.1	TSL:2	c.461C>A	p.Pro154Gln	missense	Exon 2 of 2	ENSP00000389554.1	B7Z1M9
C2CD4D	ENST00000694869.1		c.461C>A	p.Pro154Gln	missense	Exon 2 of 2	ENSP00000511552.1	B7Z1M9

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151712

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000139

AC:

166

AN:

1193416

Hom.:

Cov.:

AF XY:

0.000129

AC XY:

AN XY:

579916

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23946

American (AMR)

AF:

0.00

AC:

AN:

10836

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17166

East Asian (EAS)

AF:

0.00589

AC:

159

AN:

27000

South Asian (SAS)

AF:

0.00

AC:

AN:

48434

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3710

European-Non Finnish (NFE)

AF:

0.00000508

AC:

AN:

985198

Other (OTH)

AF:

0.0000412

AC:

AN:

48556

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000395

AC:

AN:

151820

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74200

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41498

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00117

AC:

AN:

5140

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67900

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000151

Asia WGS

AF:

0.000586

AC:

AN:

3424

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.33

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.38

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.6

PhyloP100

5.5

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.15

Sift

Benign

0.074

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.17

MutPred

0.18

Gain of MoRF binding (P = 0.0509)

MVP

0.39

ClinPred

0.98

GERP RS

3.5

Varity_R

0.18

gMVP

0.47

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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