rs718875

Variant names:

• chr1-93906464-T-C
• rs718875
• NM_002061.4:c.127-1876A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-93906464-T-C
• chr1-93906464-T-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002061.4(GCLM):​c.127-1876A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,202 control chromosomes in the GnomAD database, including 1,770 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 (1770 hom., cov: 32)
• Consequence: GCLM NM_002061.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100

Genes affected

GCLM (HGNC:4312): (glutamate-cysteine ligase modifier subunit) Glutamate-cysteine ligase, also known as gamma-glutamylcysteine synthetase, is the first rate limiting enzyme of glutathione synthesis. The enzyme consists of two subunits, a heavy catalytic subunit and a light regulatory subunit. Gamma glutamylcysteine synthetase deficiency has been implicated in some forms of hemolytic anemia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCLM	NM_002061.4	c.127-1876A>G		intron_variant	Intron 1 of 6	ENST00000370238.8	NP_002052.1
GCLM	NM_001308253.2	c.126+2574A>G		intron_variant	Intron 1 of 5		NP_001295182.1
GCLM	XM_047418031.1	c.127-1876A>G		intron_variant	Intron 1 of 6		XP_047273987.1
GCLM	XM_011541261.3	c.-138-1876A>G		intron_variant	Intron 1 of 6		XP_011539563.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCLM	ENST00000370238.8	c.127-1876A>G		intron_variant	Intron 1 of 6	1	NM_002061.4	ENSP00000359258.3
GCLM	ENST00000615724.1	c.126+2574A>G		intron_variant	Intron 1 of 5	1		ENSP00000484507.1
GCLM	ENST00000462183.1	n.261-1876A>G		intron_variant	Intron 1 of 1	3
GCLM	ENST00000467772.1	n.127-1876A>G		intron_variant	Intron 1 of 5	3

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22971 AN: 152084 Hom.: 1767 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.0586

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.151 AC: 22993 AN: 152202 Hom.: 1770 Cov.: 32 AF XY: 0.149 AC XY: 11069 AN XY: 74424

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.0584

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.157

Alfa AF: 0.0843 Hom.: 122

Bravo AF: 0.161

Asia WGS AF: 0.103 AC: 357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.8
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.44		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.44		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs718875; hg19: chr1-94372020;