rs112171353

chr7-2937118-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_032415.7(CARD11):c.1260G>A(p.Glu420=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,614,282 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0068 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00071 (9 hom.)
• Consequence: CARD11 NM_032415.7 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.18

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 7-2937118-C-T is Benign according to our data. Variant chr7-2937118-C-T is described in ClinVar as [Benign]. Clinvar id is 473927.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.18 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00679 (1034/152390) while in subpopulation AFR AF= 0.0232 (964/41598). AF 95% confidence interval is 0.022. There are 12 homozygotes in gnomad4. There are 485 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 11 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARD11	NM_032415.7	c.1260G>A	p.Glu420=	synonymous_variant	9/25	ENST00000396946.9
CARD11	NM_001324281.3	c.1260G>A	p.Glu420=	synonymous_variant	10/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD11	ENST00000396946.9	c.1260G>A	p.Glu420=	synonymous_variant	9/25	1	NM_032415.7	P1
CARD11	ENST00000698637.1	n.1586G>A		non_coding_transcript_exon_variant	9/24
CARD11	ENST00000698654.1	n.1519G>A		non_coding_transcript_exon_variant	9/10
CARD11	ENST00000698662.1	n.1460G>A		non_coding_transcript_exon_variant	9/10

Frequencies

GnomAD3 genomes AF: 0.00672 AC: 1024 AN: 152272 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0230

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00294

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00194 AC: 488 AN: 251430 Hom.: 6 AF XY: 0.00141 AC XY: 192 AN XY: 135896

Gnomad AFR exome AF: 0.0254

Gnomad AMR exome AF: 0.00162

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000967

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000713 AC: 1043 AN: 1461892 Hom.: 9 Cov.: 32 AF XY: 0.000582 AC XY: 423 AN XY: 727246

Gnomad4 AFR exome AF: 0.0225

Gnomad4 AMR exome AF: 0.00179

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000863

Gnomad4 OTH exome AF: 0.00166

GnomAD4 genome AF: 0.00679 AC: 1034 AN: 152390 Hom.: 12 Cov.: 32 AF XY: 0.00651 AC XY: 485 AN XY: 74518

Gnomad4 AFR AF: 0.0232

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00373 Hom.: 5

Bravo AF: 0.00761

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 16, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	9.5
Dann	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs112171353; hg19: chr7-2976752;