chr22-37491799-G-A

Variant names:

• chr22-37491799-G-A
• rs55875977
• NM_014550.4:c.2820C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_014550.4(CARD10):​c.2820C>T​(p.Ile940Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00922 in 1,465,622 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0084 (5 hom., cov: 27)
  • Exomes 𝑓: 0.0093 (93 hom.)
• Consequence: CARD10 NM_014550.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.426
• Publications: 3 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 22-37491799-G-A is Benign according to our data. Variant chr22-37491799-G-A is described in ClinVar as Benign. ClinVar VariationId is 716133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.426 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 5 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.2820C>T	p.Ile940Ile	synonymous	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.2820C>T	p.Ile940Ile	synonymous	Exon 19 of 20	ENSP00000251973.5	Q9BWT7-1
	CARD10	ENST00000902144.1		c.2883C>T	p.Ile961Ile	synonymous	Exon 19 of 20	ENSP00000572203.1
	CARD10	ENST00000902142.1		c.2823C>T	p.Ile941Ile	synonymous	Exon 19 of 20	ENSP00000572201.1

Frequencies

GnomAD3 genomes AF: 0.00837 AC: 1200 AN: 143334 Hom.: 5 Cov.: 27

Gnomad AFR AF: 0.00180

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00421

Gnomad ASJ AF: 0.00357

Gnomad EAS AF: 0.000236

Gnomad SAS AF: 0.00273

Gnomad FIN AF: 0.0413

Gnomad MID AF: 0.00654

Gnomad NFE AF: 0.00998

Gnomad OTH AF: 0.00598

GnomAD2 exomes AF: 0.00805 AC: 2008 AN: 249408 AF XY: 0.00819

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.00266

Gnomad ASJ exome AF: 0.00199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0332

Gnomad NFE exome AF: 0.00897

Gnomad OTH exome AF: 0.0115

GnomAD4 exome AF: 0.00931 AC: 12308 AN: 1322142 Hom.: 93 Cov.: 33 AF XY: 0.00934 AC XY: 6129 AN XY: 656326

African (AFR) AF: 0.00115 AC: 34 AN: 29462

American (AMR) AF: 0.00282 AC: 114 AN: 40438

Ashkenazi Jewish (ASJ) AF: 0.00377 AC: 80 AN: 21246

East Asian (EAS) AF: 0.00 AC: 0 AN: 27244

South Asian (SAS) AF: 0.00373 AC: 317 AN: 84994

European-Finnish (FIN) AF: 0.0429 AC: 1711 AN: 39860

Middle Eastern (MID) AF: 0.00962 AC: 48 AN: 4988

European-Non Finnish (NFE) AF: 0.00929 AC: 9499 AN: 1022644

Other (OTH) AF: 0.00985 AC: 505 AN: 51266

GnomAD4 genome AF: 0.00836 AC: 1200 AN: 143480 Hom.: 5 Cov.: 27 AF XY: 0.00925 AC XY: 644 AN XY: 69654

African (AFR) AF: 0.00180 AC: 71 AN: 39492

American (AMR) AF: 0.00420 AC: 61 AN: 14516

Ashkenazi Jewish (ASJ) AF: 0.00357 AC: 12 AN: 3358

East Asian (EAS) AF: 0.000236 AC: 1 AN: 4232

South Asian (SAS) AF: 0.00272 AC: 11 AN: 4042

European-Finnish (FIN) AF: 0.0413 AC: 376 AN: 9110

Middle Eastern (MID) AF: 0.00704 AC: 2 AN: 284

European-Non Finnish (NFE) AF: 0.00998 AC: 654 AN: 65546

Other (OTH) AF: 0.00592 AC: 12 AN: 2028

Alfa AF: 0.00662 Hom.: 1

Bravo AF: 0.00524

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0106

EpiControl AF: 0.00848

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	CARD10-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	6.0
DANN	Benign	0.81
PhyloP100		-0.43
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs55875977; hg19: chr22-37887806; COSMIC: COSV99325463; COSMIC: COSV99325463;