rs16910194

chr11-22807366-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001143830.3(GAS2):c.724-4432G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,134 control chromosomes in the GnomAD database, including 3,146 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 0.19 (3146 hom., cov: 33)
• Consequence: GAS2 NM_001143830.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

Genes affected

GAS2 (HGNC:4167): (growth arrest specific 2) The protein encoded by this gene is a caspase-3 substrate that plays a role in regulating microfilament and cell shape changes during apoptosis. It can also modulate cell susceptibility to p53-dependent apoptosis by inhibiting calpain activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAS2	NM_001143830.3	c.724-4432G>A		intron_variant		ENST00000454584.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAS2	ENST00000454584.7	c.724-4432G>A		intron_variant		1	NM_001143830.3	P1
GAS2	ENST00000278187.7	c.724-4432G>A		intron_variant		1		P1
GAS2	ENST00000524701.5	c.*364-4432G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28264 AN: 152016 Hom.: 3148 Cov.: 33

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.0403

Gnomad SAS AF: 0.0553

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.190

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.186 AC: 28281 AN: 152134 Hom.: 3146 Cov.: 33 AF XY: 0.182 AC XY: 13556 AN XY: 74374

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.0403

Gnomad4 SAS AF: 0.0552

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.191

Alfa AF: 0.158 Hom.: 2096

Bravo AF: 0.192

Asia WGS AF: 0.0900 AC: 315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.38
Dann	Benign	0.55

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: rs16910194; hg19: chr11-22828912;