chr7-2913281-G-A

Position:

chr7-2913281-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_032415.7(CARD11):c.3019+6C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00421 in 1,591,864 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 18 hom. )

Consequence

CARD11
NM_032415.7 splice_donor_region, intron

Scores

Splicing: ADA: 0.00009933

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.512

Variant links:

Genes affected

CARD11 (HGNC:16393): (caspase recruitment domain family member 11) The protein encoded by this gene belongs to the membrane-associated guanylate kinase (MAGUK) family, a class of proteins that functions as molecular scaffolds for the assembly of multiprotein complexes at specialized regions of the plasma membrane. This protein is also a member of the CARD protein family, which is defined by carrying a characteristic caspase-associated recruitment domain (CARD). This protein has a domain structure similar to that of CARD14 protein. The CARD domains of both proteins have been shown to specifically interact with BCL10, a protein known to function as a positive regulator of cell apoptosis and NF-kappaB activation. When expressed in cells, this protein activated NF-kappaB and induced the phosphorylation of BCL10. [provided by RefSeq, Jul 2008]

CARD11 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 7-2913281-G-A is Benign according to our data. Variant chr7-2913281-G-A is described in ClinVar as [Benign]. Clinvar id is 473932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00399 (602/150938) while in subpopulation AMR AF= 0.00962 (145/15070). AF 95% confidence interval is 0.00835. There are 4 homozygotes in gnomad4. There are 271 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD11	NM_032415.7 linkuse as main transcript	c.3019+6C>T		splice_donor_region_variant, intron_variant		ENST00000396946.9	NP_115791.3
CARD11	NM_001324281.3 linkuse as main transcript	c.3019+6C>T		splice_donor_region_variant, intron_variant			NP_001311210.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
CARD11	ENST00000396946.9 linkuse as main transcript	c.3019+6C>T	splice_donor_region_variant, intron_variant	1	NM_032415.7	ENSP00000380150	P1
CARD11	ENST00000698637.1 linkuse as main transcript	n.4129+6C>T	splice_donor_region_variant, intron_variant, non_coding_transcript_variant
CARD11	ENST00000698652.1 linkuse as main transcript	n.1975+6C>T	splice_donor_region_variant, intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00400

AC:

603

AN:

150820

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00970

Gnomad ASJ

AF:

0.00868

Gnomad EAS

AF:

0.00158

Gnomad SAS

AF:

0.000839

Gnomad FIN

AF:

0.00426

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00467

Gnomad OTH

AF:

0.00537

GnomAD3 exomes

AF:

0.00596

AC:

1408

AN:

236438

Hom.:

AF XY:

0.00510

AC XY:

658

AN XY:

129088

show subpopulations

Gnomad AFR exome

AF:

0.000707

Gnomad AMR exome

AF:

0.0193

Gnomad ASJ exome

AF:

0.00593

Gnomad EAS exome

AF:

0.000442

Gnomad SAS exome

AF:

0.000972

Gnomad FIN exome

AF:

0.00535

Gnomad NFE exome

AF:

0.00487

Gnomad OTH exome

AF:

0.00626

GnomAD4 exome

AF:

0.00423

AC:

6096

AN:

1440926

Hom.:

Cov.:

AF XY:

0.00409

AC XY:

2925

AN XY:

715704

show subpopulations

Gnomad4 AFR exome

AF:

0.000721

Gnomad4 AMR exome

AF:

0.0169

Gnomad4 ASJ exome

AF:

0.00696

Gnomad4 EAS exome

AF:

0.000908

Gnomad4 SAS exome

AF:

0.00102

Gnomad4 FIN exome

AF:

0.00577

Gnomad4 NFE exome

AF:

0.00415

Gnomad4 OTH exome

AF:

0.00308

GnomAD4 genome

AF:

0.00399

AC:

602

AN:

150938

Hom.:

Cov.:

AF XY:

0.00367

AC XY:

271

AN XY:

73792

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.00962

Gnomad4 ASJ

AF:

0.00868

Gnomad4 EAS

AF:

0.00158

Gnomad4 SAS

AF:

0.000840

Gnomad4 FIN

AF:

0.00426

Gnomad4 NFE

AF:

0.00467

Gnomad4 OTH

AF:

0.00531

Alfa

AF:

0.00574

Hom.:

Bravo

AF:

0.00464

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 23, 2019

- -

Severe combined immunodeficiency due to CARD11 deficiency;C4551967:BENTA disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

CARD11-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 19, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Oct 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.5

DANN

Benign

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000099

dbscSNV1_RF

Benign

0.0020

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over