rs17834873

Variant names:

• chr7-3028279-A-G
• rs17834873
• NM_032415.7:c.-126+15388T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032415.7(CARD11):​c.-126+15388T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0609 in 152,218 control chromosomes in the GnomAD database, including 351 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 0.061 (351 hom., cov: 30)
• Consequence: CARD11 NM_032415.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0805 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.-126+15388T>C		intron	N/A	NP_115791.3
	CARD11	NM_001324281.3		c.-187+15388T>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.-126+15388T>C		intron	N/A	ENSP00000380150.4	Q9BXL7
	CARD11	ENST00000911401.1		c.-126+15850T>C		intron	N/A	ENSP00000581460.1
	CARD11	ENST00000911403.1		c.-126+15388T>C		intron	N/A	ENSP00000581461.1

Frequencies

GnomAD3 genomes AF: 0.0610 AC: 9278 AN: 152100 Hom.: 352 Cov.: 30

Gnomad AFR AF: 0.0287

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0526

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0766

Gnomad FIN AF: 0.0898

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0824

Gnomad OTH AF: 0.0694

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

GnomAD4 genome AF: 0.0609 AC: 9272 AN: 152218 Hom.: 351 Cov.: 30 AF XY: 0.0617 AC XY: 4590 AN XY: 74422

African (AFR) AF: 0.0287 AC: 1194 AN: 41538

American (AMR) AF: 0.0524 AC: 802 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5174

South Asian (SAS) AF: 0.0758 AC: 365 AN: 4816

European-Finnish (FIN) AF: 0.0898 AC: 952 AN: 10606

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.0823 AC: 5599 AN: 68008

Other (OTH) AF: 0.0682 AC: 144 AN: 2110

Alfa AF: 0.0739 Hom.: 891

Bravo AF: 0.0567

Asia WGS AF: 0.0570 AC: 198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.2
DANN	Benign	0.65
PhyloP100		-0.077
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: rs17834873; hg19: chr7-3067913;