11-22807060-T-G

Position:

• chr11-22807060-T-G

Variant summary

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

The NM_001143830.3(GAS2):​c.724-4738T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,142 control chromosomes in the GnomAD database, including 1,720 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 0.15 (1720 hom., cov: 32)
• Consequence: GAS2 NM_001143830.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.762

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAS2	NM_001143830.3	c.724-4738T>G		intron_variant		ENST00000454584.7	NP_001137302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAS2	ENST00000454584.7	c.724-4738T>G		intron_variant		1	NM_001143830.3	ENSP00000401145	P1
GAS2	ENST00000278187.7	c.724-4738T>G		intron_variant		1		ENSP00000278187	P1
GAS2	ENST00000524701.5	c.*364-4738T>G		intron_variant, NMD_transcript_variant		2		ENSP00000432026

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22271 AN: 152024 Hom.: 1722 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.0398

Gnomad SAS AF: 0.0554

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.146 AC: 22274 AN: 152142 Hom.: 1720 Cov.: 32 AF XY: 0.144 AC XY: 10696 AN XY: 74384

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.0399

Gnomad4 SAS AF: 0.0553

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.158

Alfa AF: 0.138 Hom.: 913

Bravo AF: 0.144

Asia WGS AF: 0.0720 AC: 252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.57
DANN	Benign	0.42

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: rs16910190; hg19: chr11-22828606;