rs2894772

Variant names:

• chr7-2999913-A-G
• rs2894772
• NM_032415.7:c.-125-41282T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-2999913-A-G
• chr7-2999913-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• BENTA disease

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• immunodeficiency 11b with atopic dermatitis

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• severe combined immunodeficiency due to CARD11 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032415.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD11	NM_032415.7	MANE Select	c.-125-41282T>C		intron	N/A	NP_115791.3
	CARD11	NM_001324281.3		c.-186-19333T>C		intron	N/A	NP_001311210.1	Q9BXL7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD11	ENST00000396946.9	TSL:1 MANE Select	c.-125-41282T>C		intron	N/A	ENSP00000380150.4	Q9BXL7
	CARD11	ENST00000911401.1		c.-125-41282T>C		intron	N/A	ENSP00000581460.1
	CARD11	ENST00000911403.1		c.-125-41282T>C		intron	N/A	ENSP00000581461.1

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

African (AFR) AF: 0.757 AC: 30861 AN: 40772

American (AMR) AF: 0.689 AC: 10402 AN: 15094

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 2517 AN: 3456

East Asian (EAS) AF: 0.329 AC: 1640 AN: 4988

South Asian (SAS) AF: 0.723 AC: 3401 AN: 4706

European-Finnish (FIN) AF: 0.817 AC: 8346 AN: 10212

Middle Eastern (MID) AF: 0.774 AC: 226 AN: 292

European-Non Finnish (NFE) AF: 0.772 AC: 52188 AN: 67640

Other (OTH) AF: 0.730 AC: 1518 AN: 2080

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.68
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2894772; hg19: chr7-3039547;