11-105041421-A-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The ENST00000672037.1(CARD16):c.573T>G(p.Thr191=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000487 in 1,612,312 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (2 hom.)
• Consequence: CARD16 ENST00000672037.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.634

Genes affected

CARD16 (HGNC:33701): (caspase recruitment domain family member 16) Enables several functions, including CARD domain binding activity; cysteine-type endopeptidase inhibitor activity; and enzyme binding activity. Involved in several processes, including negative regulation of cysteine-type endopeptidase activity; regulation of gene expression; and regulation of signal transduction. Part of protease inhibitor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 11-105041421-A-C is Benign according to our data. Variant chr11-105041421-A-C is described in ClinVar as [Benign]. Clinvar id is 730709.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.634 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD16	ENST00000672037.1	c.573T>G	p.Thr191=	synonymous_variant	3/3			P1

Frequencies

GnomAD3 genomes AF: 0.00251 AC: 382 AN: 152156 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00864

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

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: 0.0000294

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000688 AC: 172 AN: 250180 Hom.: 2 AF XY: 0.000481 AC XY: 65 AN XY: 135204

Gnomad AFR exome AF: 0.00943

Gnomad AMR exome AF: 0.000465

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.000329

GnomAD4 exome AF: 0.000276 AC: 403 AN: 1460032 Hom.: 2 Cov.: 30 AF XY: 0.000249 AC XY: 181 AN XY: 726370

Gnomad4 AFR exome AF: 0.00943

Gnomad4 AMR exome AF: 0.000584

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000990

Gnomad4 OTH exome AF: 0.000746

GnomAD4 genome AF: 0.00251 AC: 382 AN: 152280 Hom.: 3 Cov.: 32 AF XY: 0.00243 AC XY: 181 AN XY: 74446

Gnomad4 AFR AF: 0.00861

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00126 Hom.: 0

Bravo AF: 0.00284

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 11, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	4.2
Dann	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs115095800; hg19: chr11-104912148;