rs117016854

Variant names:

• chr7-2947615-C-A
• rs117016854
• NM_032415.7:c.180G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-2947615-C-A
• chr7-2947615-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS1

The NM_032415.7(CARD11):​c.180G>T​(p.Val60Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,614,146 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00090 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (0 hom.)
• Consequence: CARD11 NM_032415.7 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.290

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant 7-2947615-C-A is Benign according to our data. Variant chr7-2947615-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 540983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.29 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0009 (137/152276) while in subpopulation AMR AF= 0.00334 (51/15288). AF 95% confidence interval is 0.00261. There are 1 homozygotes in gnomad4. There are 70 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD11	NM_032415.7	c.180G>T	p.Val60Val	synonymous_variant	Exon 3 of 25	ENST00000396946.9	NP_115791.3
CARD11	NM_001324281.3	c.180G>T	p.Val60Val	synonymous_variant	Exon 4 of 26		NP_001311210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD11	ENST00000396946.9	c.180G>T	p.Val60Val	synonymous_variant	Exon 3 of 25	1	NM_032415.7	ENSP00000380150.4

Frequencies

GnomAD3 genomes AF: 0.000907 AC: 138 AN: 152158 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00341

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000985

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.000891 AC: 224 AN: 251472 Hom.: 0 AF XY: 0.000824 AC XY: 112 AN XY: 135910

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000923

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00103 AC: 1502 AN: 1461870 Hom.: 0 Cov.: 31 AF XY: 0.000987 AC XY: 718 AN XY: 727236

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.00342

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00113

Gnomad4 OTH exome AF: 0.00136

GnomAD4 genome AF: 0.000900 AC: 137 AN: 152276 Hom.: 1 Cov.: 32 AF XY: 0.000940 AC XY: 70 AN XY: 74446

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.00334

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000985

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.000762 Hom.: 0

Bravo AF: 0.00151

EpiCase AF: 0.000818

EpiControl AF: 0.000711

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Apr 30, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Jun 08, 2022

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Severe combined immunodeficiency due to CARD11 deficiency;C4551967:BENTA disease Benign:1

Jan 26, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	5.8
DANN	Benign	0.70

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

Other links and lift over

dbSNP: rs117016854; hg19: chr7-2987249;