22-37495703-C-A

Position:

• chr22-37495703-C-A

Variant summary

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

The NM_014550.4(CARD10):​c.2303+57G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,610,918 control chromosomes in the GnomAD database, including 10,944 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 0.093 (889 hom., cov: 33)
  • Exomes 𝑓: 0.11 (10055 hom.)
• Consequence: CARD10 NM_014550.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARD10	NM_014550.4	c.2303+57G>T		intron_variant		ENST00000251973.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD10	ENST00000251973.10	c.2303+57G>T		intron_variant		1	NM_014550.4	P1

Frequencies

GnomAD3 genomes AF: 0.0929 AC: 14135 AN: 152154 Hom.: 890 Cov.: 33

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.111

GnomAD4 exome AF: 0.111 AC: 162414 AN: 1458646 Hom.: 10055 Cov.: 33 AF XY: 0.113 AC XY: 81803 AN XY: 725108

Gnomad4 AFR exome AF: 0.0206

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.140

Gnomad4 EAS exome AF: 0.271

Gnomad4 SAS exome AF: 0.152

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome AF: 0.0928 AC: 14130 AN: 152272 Hom.: 889 Cov.: 33 AF XY: 0.0945 AC XY: 7035 AN XY: 74464

Gnomad4 AFR AF: 0.0237

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0950 Hom.: 121

Bravo AF: 0.0923

Asia WGS AF: 0.201 AC: 699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.6
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2295155; hg19: chr22-37891710;