1-209675958-G-C

Variant names:

• chr1-209675958-G-C
• rs199959013
• NM_015714.4:c.274G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015714.4(G0S2):​c.274G>C​(p.Gly92Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000922 in 1,410,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G92S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000092 (0 hom.)
• Consequence: G0S2 NM_015714.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06306338).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
G0S2	NM_015714.4	c.274G>C	p.Gly92Arg	missense_variant	Exon 2 of 2	ENST00000367029.5	NP_056529.1
HSD11B1-AS1	NR_134509.1	n.97-12897C>G		intron_variant	Intron 1 of 2
HSD11B1-AS1	NR_134510.1	n.67-12897C>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
G0S2	ENST00000367029.5	c.274G>C	p.Gly92Arg	missense_variant	Exon 2 of 2	1	NM_015714.4	ENSP00000355996.4
HSD11B1-AS1	ENST00000441672.1	n.97-12897C>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000922 AC: 13 AN: 1410498 Hom.: 0 Cov.: 33 AF XY: 0.00000432 AC XY: 3 AN XY: 694436

Gnomad4 AFR exome AF: 0.0000309

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000102

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.010
DANN	Benign	0.85
DEOGEN2	Benign	0.067	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.90	L
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.026
Sift	Benign	0.073	T
Sift4G	Benign	0.43	T
Polyphen		0.0060	B
Vest4		0.10
MVP		0.095
MPC		0.67
ClinPred		0.13	T
GERP RS		-8.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.052
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs199959013; hg19: chr1-209849303;