rs570147231

Variant names:

• chr22-37491768-C-T
• rs570147231
• NM_014550.4:c.2851G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014550.4(CARD10):​c.2851G>A​(p.Val951Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,569,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000055 (0 hom., cov: 26)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: CARD10 NM_014550.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.125
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03396955).

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.2851G>A	p.Val951Ile	missense	Exon 19 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.2851G>A	p.Val951Ile	missense	Exon 19 of 20	ENSP00000251973.5	Q9BWT7-1
	CARD10	ENST00000902144.1		c.2914G>A	p.Val972Ile	missense	Exon 19 of 20	ENSP00000572203.1
	CARD10	ENST00000902142.1		c.2854G>A	p.Val952Ile	missense	Exon 19 of 20	ENSP00000572201.1

Frequencies

GnomAD3 genomes AF: 0.0000547 AC: 8 AN: 146192 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.0000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000903

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000803 AC: 20 AN: 248988 AF XY: 0.0000667

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000164 AC: 233 AN: 1423720 Hom.: 0 Cov.: 28 AF XY: 0.000169 AC XY: 120 AN XY: 709664

African (AFR) AF: 0.00 AC: 0 AN: 32570

American (AMR) AF: 0.00 AC: 0 AN: 44364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25532

East Asian (EAS) AF: 0.00 AC: 0 AN: 39054

South Asian (SAS) AF: 0.00 AC: 0 AN: 85682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5668

European-Non Finnish (NFE) AF: 0.000213 AC: 230 AN: 1080796

Other (OTH) AF: 0.0000510 AC: 3 AN: 58854

GnomAD4 genome AF: 0.0000547 AC: 8 AN: 146192 Hom.: 0 Cov.: 26 AF XY: 0.0000563 AC XY: 4 AN XY: 71052

African (AFR) AF: 0.0000507 AC: 2 AN: 39480

American (AMR) AF: 0.00 AC: 0 AN: 14662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3426

East Asian (EAS) AF: 0.00 AC: 0 AN: 4700

South Asian (SAS) AF: 0.00 AC: 0 AN: 4450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.0000903 AC: 6 AN: 66418

Other (OTH) AF: 0.00 AC: 0 AN: 2004

Alfa AF: 0.000121 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.0000545

EpiControl AF: 0.000357

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.29
DEOGEN2	Benign	0.073	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.54	N
PhyloP100		0.13
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.025
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.28
MVP		0.24
MPC		0.26
ClinPred		0.027	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.031
gMVP		0.23
Mutation Taster		=99/1	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: rs570147231; hg19: chr22-37887775;