Variant 5-40843448-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_032587.4(CARD6):c.580A>G(p.Ile194Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,613,748 control chromosomes in the GnomAD database, including 146 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 0.0080 ( 6 hom., cov: 33)

Exomes 𝑓: 0.012 ( 140 hom. )

Consequence

CARD6
NM_032587.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.33

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023836493).

BP6

Variant 5-40843448-A-G is Benign according to our data. Variant chr5-40843448-A-G is described in ClinVar as [Benign]. Clinvar id is 787618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD6	NM_032587.4 linkuse as main transcript	c.580A>G	p.Ile194Val	missense_variant	2/3	ENST00000254691.10	NP_115976.2	Q9BX69
CARD6	XM_017009989.2 linkuse as main transcript	c.283+1783A>G		intron_variant			XP_016865478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD6	ENST00000254691.10 linkuse as main transcript	c.580A>G	p.Ile194Val	missense_variant	2/3	1	NM_032587.4	ENSP00000254691.5		Q9BX69
CARD6	ENST00000381677.4 linkuse as main transcript	c.580A>G	p.Ile194Val	missense_variant	2/3	1		ENSP00000371093.3		A0A0B4J1T5

Frequencies

GnomAD3 genomes

AF:

0.00799

AC:

1217

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00207

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.0175

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0123

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00862

AC:

2157

AN:

250260

Hom.:

AF XY:

0.00820

AC XY:

1109

AN XY:

135288

show subpopulations

Gnomad AFR exome

AF:

0.00167

Gnomad AMR exome

AF:

0.00279

Gnomad ASJ exome

AF:

0.0000999

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00118

Gnomad FIN exome

AF:

0.0220

Gnomad NFE exome

AF:

0.0130

Gnomad OTH exome

AF:

0.00772

GnomAD4 exome

AF:

0.0123

AC:

17917

AN:

1461372

Hom.:

140

Cov.:

AF XY:

0.0116

AC XY:

8455

AN XY:

726962

show subpopulations

Gnomad4 AFR exome

AF:

0.00188

Gnomad4 AMR exome

AF:

0.00278

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00131

Gnomad4 FIN exome

AF:

0.0211

Gnomad4 NFE exome

AF:

0.0142

Gnomad4 OTH exome

AF:

0.0106

GnomAD4 genome

AF:

0.00799

AC:

1217

AN:

152376

Hom.:

Cov.:

AF XY:

0.00793

AC XY:

591

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.00207

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.0175

Gnomad4 NFE

AF:

0.0123

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.00707

TwinsUK

AF:

0.0151

AC:

ALSPAC

AF:

0.0153

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0130

AC:

112

ExAC

AF:

0.00872

AC:

1059

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0120

EpiControl

AF:

0.0128

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 24, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0038

T;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.49

T;T

MetaRNN

Benign

0.0024

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.51

N;N

REVEL

Benign

0.037

Sift

Uncertain

0.0080

D;D

Sift4G

Benign

0.069

T;T

Polyphen

0.0020

B;.

Vest4

0.16

MVP

0.14

MPC

0.025

ClinPred

0.018

GERP RS

4.1

Varity_R

0.063

gMVP

0.077

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over