rs2295155

Variant names:

• chr22-37495703-C-A
• rs2295155
• NM_014550.4:c.2303+57G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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 -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 rank	MANE	Protein	UniProt
CARD10	NM_014550.4	c.2303+57G>T		intron_variant	Intron 14 of 19	ENST00000251973.10	NP_055365.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD10	ENST00000251973.10	c.2303+57G>T		intron_variant	Intron 14 of 19	1	NM_014550.4	ENSP00000251973.5

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

African (AFR) AF: 0.0206 AC: 687 AN: 33424

American (AMR) AF: 0.136 AC: 6084 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 3645 AN: 26066

East Asian (EAS) AF: 0.271 AC: 10742 AN: 39644

South Asian (SAS) AF: 0.152 AC: 13068 AN: 86206

European-Finnish (FIN) AF: 0.103 AC: 5433 AN: 52936

Middle Eastern (MID) AF: 0.192 AC: 1100 AN: 5744

European-Non Finnish (NFE) AF: 0.103 AC: 114539 AN: 1109690

Other (OTH) AF: 0.118 AC: 7116 AN: 60264

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

African (AFR) AF: 0.0237 AC: 985 AN: 41578

American (AMR) AF: 0.118 AC: 1808 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 485 AN: 3472

East Asian (EAS) AF: 0.254 AC: 1309 AN: 5162

South Asian (SAS) AF: 0.150 AC: 724 AN: 4830

European-Finnish (FIN) AF: 0.104 AC: 1105 AN: 10606

Middle Eastern (MID) AF: 0.190 AC: 55 AN: 290

European-Non Finnish (NFE) AF: 0.108 AC: 7318 AN: 68000

Other (OTH) AF: 0.115 AC: 243 AN: 2114

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
PhyloP100		-0.085
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2295155; hg19: chr22-37891710;