7-2999913-A-G

Position:

• chr7-2999913-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032415.7(CARD11):​c.-125-41282T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 150,144 control chromosomes in the GnomAD database, including 42,062 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.74 (42062 hom., cov: 26)
• Consequence: CARD11 NM_032415.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD11	NM_032415.7	c.-125-41282T>C		intron_variant		ENST00000396946.9	NP_115791.3
CARD11	NM_001324281.3	c.-186-19333T>C		intron_variant			NP_001311210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD11	ENST00000396946.9	c.-125-41282T>C		intron_variant		1	NM_032415.7	ENSP00000380150.4
CARD11	ENST00000356408.3	c.-186-19333T>C		intron_variant		3		ENSP00000348779.3
CARD11	ENST00000698637.1	n.202-41282T>C		intron_variant
CARD11	ENST00000698654.1	n.101-41282T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.745 AC: 111760 AN: 150036 Hom.: 42027 Cov.: 26

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.783

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.737

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.745 AC: 111843 AN: 150144 Hom.: 42062 Cov.: 26 AF XY: 0.742 AC XY: 54347 AN XY: 73204

Gnomad4 AFR AF: 0.757

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.728

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.817

Gnomad4 NFE AF: 0.772

Gnomad4 OTH AF: 0.730

Alfa AF: 0.767 Hom.: 5271

Bravo AF: 0.734

Asia WGS AF: 0.553 AC: 1919 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.68

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: rs2894772; hg19: chr7-3039547;