22-37492762-C-T

Variant names:

• chr22-37492762-C-T
• rs377009692
• NM_014550.4:c.2517G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The ENST00000437756.5(CARD10):​c.1440G>A​(p.Pro480Pro) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,612,794 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00094 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (39 hom.)
• Consequence: CARD10 ENST00000437756.5 splice_region, synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -5.65
• Publications: 2 publications found

Genes affected

CARD10 (HGNC:16422): (caspase recruitment domain family member 10) The caspase recruitment domain (CARD) is a protein module that consists of 6 or 7 antiparallel alpha helices. It participates in apoptosis signaling through highly specific protein-protein homophilic interactions. Like several other CARD proteins, CARD10 belongs to the membrane-associated guanylate kinase (MAGUK) family and activates NF-kappa-B (NFKB; see MIM 164011) through BCL10 (MIM 603517) (Wang et al., 2001 [PubMed 11259443]).[supplied by OMIM, Mar 2008]

CARD10 Gene-Disease associations (from GenCC):

• immunodeficiency 89 and autoimmunity

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 22-37492762-C-T is Benign according to our data. Variant chr22-37492762-C-T is described in ClinVar as Benign. ClinVar VariationId is 3044055.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-5.65 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000939 (143/152264) while in subpopulation SAS AF = 0.0276 (133/4826). AF 95% confidence interval is 0.0237. There are 1 homozygotes in GnomAd4. There are 97 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 39 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000437756.5. 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
	CARD10	NM_014550.4	MANE Select	c.2517G>A	p.Pro839Pro	synonymous	Exon 17 of 20	NP_055365.2	Q9BWT7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD10	ENST00000251973.10	TSL:1 MANE Select	c.2517G>A	p.Pro839Pro	synonymous	Exon 17 of 20	ENSP00000251973.5	Q9BWT7-1
	CARD10	ENST00000437756.5	TSL:1	c.1440G>A	p.Pro480Pro	splice_region synonymous	Exon 15 of 15	ENSP00000416239.1	B0QYC4
	CARD10	ENST00000902144.1		c.2580G>A	p.Pro860Pro	synonymous	Exon 17 of 20	ENSP00000572203.1

Frequencies

GnomAD3 genomes AF: 0.000940 AC: 143 AN: 152146 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0275

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00372 AC: 922 AN: 247928 AF XY: 0.00496

Gnomad AFR exome AF: 0.0000627

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000449

Gnomad OTH exome AF: 0.00264

GnomAD4 exome AF: 0.00175 AC: 2552 AN: 1460530 Hom.: 39 Cov.: 32 AF XY: 0.00251 AC XY: 1827 AN XY: 726590

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.0278 AC: 2394 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52286

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5762

European-Non Finnish (NFE) AF: 0.0000243 AC: 27 AN: 1111886

Other (OTH) AF: 0.00200 AC: 121 AN: 60366

GnomAD4 genome AF: 0.000939 AC: 143 AN: 152264 Hom.: 1 Cov.: 32 AF XY: 0.00130 AC XY: 97 AN XY: 74450

African (AFR) AF: 0.000120 AC: 5 AN: 41552

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.0276 AC: 133 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68000

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.000171 Hom.: 0

Bravo AF: 0.000234

Asia WGS AF: 0.0130 AC: 45 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CARD10-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.18
DANN	Benign	0.92
PhyloP100		-5.7
Mutation Taster		=99/1	polymorphism

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: rs377009692; hg19: chr22-37888769; COSMIC: COSV52654082; COSMIC: COSV52654082;