rs184926618

Positions:

• chr7-2913280-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_032415.7(CARD11):​c.3019+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000264 in 1,588,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: CARD11 NM_032415.7 splice_region, intron
• Scores: Splicing: ADA: 0.00001580
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.232

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-2913280-C-T is Benign according to our data. Variant chr7-2913280-C-T is described in ClinVar as [Benign]. Clinvar id is 540985.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00154 (231/150342) while in subpopulation AFR AF= 0.00529 (218/41188). AF 95% confidence interval is 0.00472. There are 0 homozygotes in gnomad4. There are 107 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD11	NM_032415.7	c.3019+7G>A		splice_region_variant, intron_variant		ENST00000396946.9	NP_115791.3
CARD11	NM_001324281.3	c.3019+7G>A		splice_region_variant, intron_variant			NP_001311210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD11	ENST00000396946.9	c.3019+7G>A		splice_region_variant, intron_variant		1	NM_032415.7	ENSP00000380150.4
CARD11	ENST00000698637.1	n.4129+7G>A		splice_region_variant, intron_variant
CARD11	ENST00000698652.1	n.1975+7G>A		splice_region_variant, intron_variant

Frequencies

GnomAD3 genomes AF: 0.00154 AC: 231 AN: 150228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000600

Gnomad ASJ AF: 0.000291

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000211

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000298

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000275 AC: 65 AN: 236492 Hom.: 0 AF XY: 0.000163 AC XY: 21 AN XY: 129028

Gnomad AFR exome AF: 0.00380

Gnomad AMR exome AF: 0.0000585

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: 0.0000373

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000131 AC: 189 AN: 1437902 Hom.: 0 Cov.: 32 AF XY: 0.000102 AC XY: 73 AN XY: 714042

Gnomad4 AFR exome AF: 0.00365

Gnomad4 AMR exome AF: 0.0000680

Gnomad4 ASJ exome AF: 0.0000394

Gnomad4 EAS exome AF: 0.0000264

Gnomad4 SAS exome AF: 0.0000471

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000409

Gnomad4 OTH exome AF: 0.000236

GnomAD4 genome AF: 0.00154 AC: 231 AN: 150342 Hom.: 0 Cov.: 32 AF XY: 0.00146 AC XY: 107 AN XY: 73514

Gnomad4 AFR AF: 0.00529

Gnomad4 AMR AF: 0.000599

Gnomad4 ASJ AF: 0.000291

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000212

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000298

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000641 Hom.: 0

Bravo AF: 0.00169

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 20, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.026
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
dbscSNV1_RF	Benign	0.012
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: rs184926618; hg19: chr7-2952914;