Variant rs10512747 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000254691.10(CARD6):c.257C>T(p.Ser86Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,613,284 control chromosomes in the GnomAD database, including 10,399 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.082 ( 696 hom., cov: 33)

Exomes 𝑓: 0.11 ( 9703 hom. )

Consequence

CARD6
ENST00000254691.10 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.548

Variant links:

Genes affected

CARD6 (HGNC:16394): (caspase recruitment domain family member 6) This gene encodes a protein that contains a caspase recruitment domain (CARD), an antiparallel six-helical bundle that mediates homotypic protein-protein interactions. The encoded protein is a microtubule-associated protein that has been shown to interact with receptor-interacting protein kinases and positively modulate signal transduction pathways converging on activation of the inducible transcription factor NF-kB. [provided by RefSeq, Jul 2008]

CARD6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015994012).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD6	NM_032587.4 linkuse as main transcript	c.257C>T	p.Ser86Leu	missense_variant	1/3	ENST00000254691.10	NP_115976.2
CARD6	XM_017009989.2 linkuse as main transcript	c.257C>T	p.Ser86Leu	missense_variant	1/2		XP_016865478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD6	ENST00000254691.10 linkuse as main transcript	c.257C>T	p.Ser86Leu	missense_variant	1/3	1	NM_032587.4	ENSP00000254691	P3
CARD6	ENST00000381677.4 linkuse as main transcript	c.257C>T	p.Ser86Leu	missense_variant	1/3	1		ENSP00000371093	A2

Frequencies

GnomAD3 genomes

AF:

0.0823

AC:

12513

AN:

152040

Hom.:

696

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0218

Gnomad AMI

AF:

0.0429

Gnomad AMR

AF:

0.0828

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.00328

Gnomad SAS

AF:

0.0576

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.121

Gnomad OTH

AF:

0.0907

GnomAD3 exomes

AF:

0.0905

AC:

22513

AN:

248684

Hom.:

1266

AF XY:

0.0942

AC XY:

12685

AN XY:

134730

show subpopulations

Gnomad AFR exome

AF:

0.0217

Gnomad AMR exome

AF:

0.0573

Gnomad ASJ exome

AF:

0.109

Gnomad EAS exome

AF:

0.00240

Gnomad SAS exome

AF:

0.0651

Gnomad FIN exome

AF:

0.106

Gnomad NFE exome

AF:

0.127

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.110

AC:

160815

AN:

1461126

Hom.:

9703

Cov.:

AF XY:

0.109

AC XY:

79562

AN XY:

726860

show subpopulations

Gnomad4 AFR exome

AF:

0.0166

Gnomad4 AMR exome

AF:

0.0597

Gnomad4 ASJ exome

AF:

0.106

Gnomad4 EAS exome

AF:

0.00139

Gnomad4 SAS exome

AF:

0.0662

Gnomad4 FIN exome

AF:

0.107

Gnomad4 NFE exome

AF:

0.123

Gnomad4 OTH exome

AF:

0.104

GnomAD4 genome

AF:

0.0822

AC:

12510

AN:

152158

Hom.:

696

Cov.:

AF XY:

0.0800

AC XY:

5952

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0218

Gnomad4 AMR

AF:

0.0826

Gnomad4 ASJ

AF:

0.118

Gnomad4 EAS

AF:

0.00328

Gnomad4 SAS

AF:

0.0568

Gnomad4 FIN

AF:

0.106

Gnomad4 NFE

AF:

0.122

Gnomad4 OTH

AF:

0.0898

Alfa

AF:

0.114

Hom.:

2654

Bravo

AF:

0.0765

TwinsUK

AF:

0.117

AC:

434

ALSPAC

AF:

0.128

AC:

495

ESP6500AA

AF:

0.0245

AC:

108

ESP6500EA

AF:

0.120

AC:

1036

ExAC

AF:

0.0910

AC:

11047

Asia WGS

AF:

0.0380

AC:

133

AN:

3478

EpiCase

AF:

0.125

EpiControl

AF:

0.127

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.018

T;T

Eigen

Benign

0.17

Eigen_PC

Benign

0.067

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.81

T;T

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

0.87

P;P

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.091

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.99

D;.

Vest4

0.26

MPC

0.18

ClinPred

0.030

GERP RS

4.0

Varity_R

0.33

gMVP

0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over