rs2527509

Variant names:

• chr7-2923119-G-A
• rs2527509
• NM_032415.7:c.2142+13C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-2923119-G-A
• chr7-2923119-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032415.7(CARD11):​c.2142+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 1,606,740 control chromosomes in the GnomAD database, including 440,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (32710 hom., cov: 34)
  • Exomes 𝑓: 0.74 (407908 hom.)
• Consequence: CARD11 NM_032415.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.293
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-2923119-G-A is Benign according to our data. Variant chr7-2923119-G-A is described in ClinVar as Benign. ClinVar VariationId is 402479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.2142+13C>T		intron	N/A	NP_115791.3
	CARD11	NM_001324281.3		c.2142+13C>T		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.2142+13C>T		intron	N/A	ENSP00000380150.4	Q9BXL7
	CARD11	ENST00000888804.1		c.2142+13C>T		intron	N/A	ENSP00000558863.1
	CARD11	ENST00000888805.1		c.2142+13C>T		intron	N/A	ENSP00000558864.1

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95577 AN: 152080 Hom.: 32712 Cov.: 34

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.642

GnomAD2 exomes AF: 0.676 AC: 164061 AN: 242524 AF XY: 0.683

Gnomad AFR exome AF: 0.347

Gnomad AMR exome AF: 0.634

Gnomad ASJ exome AF: 0.731

Gnomad EAS exome AF: 0.382

Gnomad FIN exome AF: 0.815

Gnomad NFE exome AF: 0.770

Gnomad OTH exome AF: 0.717

GnomAD4 exome AF: 0.742 AC: 1078948 AN: 1454542 Hom.: 407908 Cov.: 35 AF XY: 0.740 AC XY: 535119 AN XY: 723610

African (AFR) AF: 0.341 AC: 11370 AN: 33388

American (AMR) AF: 0.633 AC: 28195 AN: 44570

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 18902 AN: 26072

East Asian (EAS) AF: 0.412 AC: 16325 AN: 39596

South Asian (SAS) AF: 0.625 AC: 53743 AN: 86004

European-Finnish (FIN) AF: 0.815 AC: 40676 AN: 49912

Middle Eastern (MID) AF: 0.725 AC: 3900 AN: 5380

European-Non Finnish (NFE) AF: 0.778 AC: 863311 AN: 1109442

Other (OTH) AF: 0.707 AC: 42526 AN: 60178

GnomAD4 genome AF: 0.628 AC: 95598 AN: 152198 Hom.: 32710 Cov.: 34 AF XY: 0.627 AC XY: 46637 AN XY: 74402

African (AFR) AF: 0.357 AC: 14817 AN: 41530

American (AMR) AF: 0.650 AC: 9940 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2530 AN: 3472

East Asian (EAS) AF: 0.382 AC: 1966 AN: 5150

South Asian (SAS) AF: 0.602 AC: 2905 AN: 4826

European-Finnish (FIN) AF: 0.820 AC: 8705 AN: 10610

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52446 AN: 68008

Other (OTH) AF: 0.638 AC: 1348 AN: 2112

Alfa AF: 0.719 Hom.: 9922

Bravo AF: 0.603

Asia WGS AF: 0.501 AC: 1741 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	BENTA disease (1)
-	-	1	Immunodeficiency 11b with atopic dermatitis (1)
-	-	1	not provided (1)
-	-	1	Severe combined immunodeficiency due to CARD11 deficiency (1)
-	-	1	Severe combined immunodeficiency due to CARD11 deficiency;C4551967:BENTA disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.63
PhyloP100		-0.29
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: rs2527509; hg19: chr7-2962753; COSMIC: COSV62755629; COSMIC: COSV62755629;