NM_014550.4:c.1384-207G>C

Variant names:

• chr22-37504976-C-G
• rs9610774
• NM_014550.4:c.1384-207G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014550.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD10	NM_014550.4	MANE Select	c.1384-207G>C		intron	N/A	NP_055365.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD10	ENST00000251973.10	TSL:1 MANE Select	c.1384-207G>C		intron	N/A	ENSP00000251973.5
	CARD10	ENST00000437756.5	TSL:1	c.307-207G>C		intron	N/A	ENSP00000416239.1
	CARD10	ENST00000403299.5	TSL:5	c.1384-207G>C		intron	N/A	ENSP00000384570.1

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

African (AFR) AF: 0.379 AC: 15749 AN: 41504

American (AMR) AF: 0.139 AC: 2126 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 770 AN: 3470

East Asian (EAS) AF: 0.182 AC: 939 AN: 5168

South Asian (SAS) AF: 0.256 AC: 1235 AN: 4816

European-Finnish (FIN) AF: 0.160 AC: 1695 AN: 10586

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8711 AN: 67998

Other (OTH) AF: 0.206 AC: 434 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.20
DANN	Benign	0.47
PhyloP100		-1.1
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: rs9610774; hg19: chr22-37900983; COSMIC: COSV52660320; COSMIC: COSV52660320;