1-209676061-T-G

Position:

• chr1-209676061-T-G

Variant summary

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

The NM_015714.4(G0S2):​c.*65T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.974 in 1,320,082 control chromosomes in the GnomAD database, including 627,454 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 0.97 (71765 hom., cov: 33)
  • Exomes 𝑓: 0.97 (555689 hom.)
• Consequence: G0S2 NM_015714.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

Genes affected

G0S2 (HGNC:30229): (G0/G1 switch 2) Involved in extrinsic apoptotic signaling pathway and positive regulation of extrinsic apoptotic signaling pathway. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

HSD11B1-AS1 (HGNC:54053): (HSD11B1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
G0S2	NM_015714.4	c.*65T>G		3_prime_UTR_variant	2/2	ENST00000367029.5
HSD11B1-AS1	NR_134510.1	n.67-13000A>C		intron_variant, non_coding_transcript_variant
HSD11B1-AS1	NR_134509.1	n.97-13000A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
G0S2	ENST00000367029.5	c.*65T>G		3_prime_UTR_variant	2/2	1	NM_015714.4	P1
HSD11B1-AS1	ENST00000441672.1	n.97-13000A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.969 AC: 147467 AN: 152146 Hom.: 71706 Cov.: 33

Gnomad AFR AF: 0.994

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.994

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.989

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.985

Gnomad OTH AF: 0.972

GnomAD4 exome AF: 0.974 AC: 1137789 AN: 1167818 Hom.: 555689 Cov.: 15 AF XY: 0.974 AC XY: 559706 AN XY: 574596

Gnomad4 AFR exome AF: 0.996

Gnomad4 AMR exome AF: 0.854

Gnomad4 ASJ exome AF: 0.995

Gnomad4 EAS exome AF: 0.739

Gnomad4 SAS exome AF: 0.959

Gnomad4 FIN exome AF: 0.988

Gnomad4 NFE exome AF: 0.987

Gnomad4 OTH exome AF: 0.968

GnomAD4 genome AF: 0.969 AC: 147584 AN: 152264 Hom.: 71765 Cov.: 33 AF XY: 0.966 AC XY: 71908 AN XY: 74450

Gnomad4 AFR AF: 0.994

Gnomad4 AMR AF: 0.893

Gnomad4 ASJ AF: 0.994

Gnomad4 EAS AF: 0.741

Gnomad4 SAS AF: 0.953

Gnomad4 FIN AF: 0.989

Gnomad4 NFE AF: 0.985

Gnomad4 OTH AF: 0.972

Alfa AF: 0.977 Hom.: 49538

Bravo AF: 0.962

Asia WGS AF: 0.878 AC: 3053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.5
DANN	Benign	0.34

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: rs1473683; hg19: chr1-209849406; COSMIC: COSV65433122; COSMIC: COSV65433122;