chr22-37491181-C-T

Variant names:

• chr22-37491181-C-T
• rs151290630
• NM_014550.4:c.3077G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_014550.4(CARD10):​c.3077G>A​(p.Cys1026Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000542 in 1,567,024 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00053 (6 hom.)
• Consequence: CARD10 NM_014550.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.178
• 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032688975).
• BP6: Variant 22-37491181-C-T is Benign according to our data. Variant chr22-37491181-C-T is described in ClinVar as Benign. ClinVar VariationId is 3040877.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 6 Unknown gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD10	NM_014550.4	MANE Select	c.3077G>A	p.Cys1026Tyr	missense	Exon 20 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.3077G>A	p.Cys1026Tyr	missense	Exon 20 of 20	ENSP00000251973.5	Q9BWT7-1
	CARD10	ENST00000902144.1		c.3140G>A	p.Cys1047Tyr	missense	Exon 20 of 20	ENSP00000572203.1
	CARD10	ENST00000902142.1		c.3080G>A	p.Cys1027Tyr	missense	Exon 20 of 20	ENSP00000572201.1

Frequencies

GnomAD3 genomes AF: 0.000664 AC: 101 AN: 152088 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00130 AC: 228 AN: 174846 AF XY: 0.00124

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000222

Gnomad ASJ exome AF: 0.00396

Gnomad EAS exome AF: 0.0130

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000819

Gnomad OTH exome AF: 0.00150

GnomAD4 exome AF: 0.000529 AC: 748 AN: 1414818 Hom.: 6 Cov.: 31 AF XY: 0.000543 AC XY: 380 AN XY: 699960

African (AFR) AF: 0.0000306 AC: 1 AN: 32632

American (AMR) AF: 0.000158 AC: 6 AN: 38088

Ashkenazi Jewish (ASJ) AF: 0.00586 AC: 148 AN: 25242

East Asian (EAS) AF: 0.0135 AC: 506 AN: 37510

South Asian (SAS) AF: 0.0000619 AC: 5 AN: 80784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.0000202 AC: 22 AN: 1089702

Other (OTH) AF: 0.00102 AC: 60 AN: 58640

GnomAD4 genome AF: 0.000664 AC: 101 AN: 152206 Hom.: 0 Cov.: 31 AF XY: 0.000739 AC XY: 55 AN XY: 74420

African (AFR) AF: 0.0000241 AC: 1 AN: 41556

American (AMR) AF: 0.000523 AC: 8 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3472

East Asian (EAS) AF: 0.0133 AC: 68 AN: 5116

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67992

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000541 Hom.: 0

Bravo AF: 0.000665

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000119 AC: 1

ExAC AF: 0.000785 AC: 92

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

ClinVar submissions

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
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.98
DANN	Benign	0.74
DEOGEN2	Benign	0.064	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.18
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.061
Sift	Benign	0.55	T
Sift4G	Benign	0.60	T
Polyphen		0.012	B
Vest4		0.068
MVP		0.12
MPC		0.59
ClinPred		0.0044	T
GERP RS		3.1
Varity_R		0.019
gMVP		0.36
Mutation Taster		=100/0	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: rs151290630; hg19: chr22-37887219; COSMIC: COSV107248647; COSMIC: COSV107248647;