11-22680004-T-C

Variant names:

• chr11-22680004-T-C
• rs426344
• NM_001143830.3:c.145+4990T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001143830.3(GAS2):​c.145+4990T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.925 in 152,088 control chromosomes in the GnomAD database, including 65,377 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 0.92 (65377 hom., cov: 32)
• Consequence: GAS2 NM_001143830.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500
• Publications: 0 publications found

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]

GAS2 Gene-Disease associations (from GenCC):

• hearing loss disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• hearing loss, autosomal recessive 125

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143830.3. 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
	GAS2	NM_001143830.3	MANE Select	c.145+4990T>C		intron	N/A	NP_001137302.1	O43903-1
	GAS2	NM_001391933.1		c.145+4990T>C		intron	N/A	NP_001378862.1
	GAS2	NM_001391934.1		c.145+4990T>C		intron	N/A	NP_001378863.1	O43903-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS2	ENST00000454584.7	TSL:1 MANE Select	c.145+4990T>C		intron	N/A	ENSP00000401145.2	O43903-1
	GAS2	ENST00000278187.7	TSL:1	c.145+4990T>C		intron	N/A	ENSP00000278187.3	O43903-1
	GAS2	ENST00000867053.1		c.145+4990T>C		intron	N/A	ENSP00000537112.1

Frequencies

GnomAD3 genomes AF: 0.925 AC: 140552 AN: 151970 Hom.: 65347 Cov.: 32

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 0.933

Gnomad SAS AF: 0.988

Gnomad FIN AF: 0.976

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.941

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

GnomAD4 genome AF: 0.925 AC: 140641 AN: 152088 Hom.: 65377 Cov.: 32 AF XY: 0.926 AC XY: 68829 AN XY: 74342

African (AFR) AF: 0.818 AC: 33918 AN: 41442

American (AMR) AF: 0.928 AC: 14166 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.988 AC: 3432 AN: 3472

East Asian (EAS) AF: 0.933 AC: 4836 AN: 5182

South Asian (SAS) AF: 0.988 AC: 4767 AN: 4824

European-Finnish (FIN) AF: 0.976 AC: 10351 AN: 10602

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.971 AC: 65979 AN: 67974

Other (OTH) AF: 0.942 AC: 1991 AN: 2114

Alfa AF: 0.940 Hom.: 8719

Bravo AF: 0.914

Asia WGS AF: 0.936 AC: 3250 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.4
DANN	Benign	0.69
PhyloP100		-0.050
Mutation Taster		=100/0	polymorphism (auto)

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: rs426344; hg19: chr11-22701550;