rs142108678

chr7-2937166-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_032415.7(CARD11):c.1212G>A(p.Arg404=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00268 in 1,614,272 control chromosomes in the GnomAD database, including 157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0055 (28 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (129 hom.)
• Consequence: CARD11 NM_032415.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.258

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 7-2937166-C-T is Benign according to our data. Variant chr7-2937166-C-T is described in ClinVar as [Benign]. Clinvar id is 434567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.258 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARD11	NM_032415.7	c.1212G>A	p.Arg404=	synonymous_variant	9/25	ENST00000396946.9
CARD11	NM_001324281.3	c.1212G>A	p.Arg404=	synonymous_variant	10/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD11	ENST00000396946.9	c.1212G>A	p.Arg404=	synonymous_variant	9/25	1	NM_032415.7	P1
CARD11	ENST00000698637.1	n.1538G>A		non_coding_transcript_exon_variant	9/24
CARD11	ENST00000698654.1	n.1471G>A		non_coding_transcript_exon_variant	9/10
CARD11	ENST00000698662.1	n.1412G>A		non_coding_transcript_exon_variant	9/10

Frequencies

GnomAD3 genomes AF: 0.00552 AC: 841 AN: 152270 Hom.: 28 Cov.: 32

Gnomad AFR AF: 0.000989

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0514

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.0110 AC: 2774 AN: 251484 Hom.: 104 AF XY: 0.00837 AC XY: 1137 AN XY: 135918

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.0788

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00472

GnomAD4 exome AF: 0.00238 AC: 3475 AN: 1461884 Hom.: 129 Cov.: 33 AF XY: 0.00202 AC XY: 1471 AN XY: 727240

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.0745

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000403

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.00162

GnomAD4 genome AF: 0.00554 AC: 844 AN: 152388 Hom.: 28 Cov.: 32 AF XY: 0.00635 AC XY: 473 AN XY: 74512

Gnomad4 AFR AF: 0.000986

Gnomad4 AMR AF: 0.0515

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.000948 Hom.: 3

Bravo AF: 0.00901

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 20, 2020

- -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	8.9
Dann	Benign	0.76

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: rs142108678; hg19: chr7-2976800;