22-37504976-C-G

Position:

• chr22-37504976-C-G

Variant summary

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

The NM_014550.4(CARD10):​c.1384-207G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,136 control chromosomes in the GnomAD database, including 4,302 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 0.21 (4302 hom., cov: 32)
• Consequence: CARD10 NM_014550.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD10	NM_014550.4	c.1384-207G>C		intron_variant		ENST00000251973.10	NP_055365.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD10	ENST00000251973.10	c.1384-207G>C		intron_variant		1	NM_014550.4	ENSP00000251973	P1
CARD10	ENST00000437756.5	c.307-207G>C		intron_variant		1		ENSP00000416239
CARD10	ENST00000403299.5	c.1384-207G>C		intron_variant		5		ENSP00000384570	P1
CARD10	ENST00000406271.7	c.526-207G>C		intron_variant		2		ENSP00000385799

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31789 AN: 152018 Hom.: 4291 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.209 AC: 31829 AN: 152136 Hom.: 4302 Cov.: 32 AF XY: 0.209 AC XY: 15509 AN XY: 74372

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.206

Alfa AF: 0.0865 Hom.: 123

Bravo AF: 0.213

Asia WGS AF: 0.214 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.20
DANN	Benign	0.47

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: rs9610774; hg19: chr22-37900983; COSMIC: COSV52660320; COSMIC: COSV52660320;