1-93899778-C-A

Variant names:

• chr1-93899778-C-A
• rs7517826
• NM_002061.4:c.277+1807G>T

Variant summary

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

The ENST00000370238.8(GCLM):​c.277+1807G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,808 control chromosomes in the GnomAD database, including 16,887 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 0.44 (16887 hom., cov: 31)
• Consequence: GCLM ENST00000370238.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152
• Publications: 9 publications found

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]

ENSG00000310419 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000370238.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCLM	NM_002061.4	MANE Select	c.277+1807G>T		intron	N/A	NP_002052.1
	GCLM	NM_001308253.2		c.211+1807G>T		intron	N/A	NP_001295182.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCLM	ENST00000370238.8	TSL:1 MANE Select	c.277+1807G>T		intron	N/A	ENSP00000359258.3
	GCLM	ENST00000615724.1	TSL:1	c.211+1807G>T		intron	N/A	ENSP00000484507.1
	GCLM	ENST00000467772.1	TSL:3	n.277+1807G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67455 AN: 151692 Hom.: 16852 Cov.: 31

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.445 AC: 67545 AN: 151808 Hom.: 16887 Cov.: 31 AF XY: 0.442 AC XY: 32820 AN XY: 74170

African (AFR) AF: 0.681 AC: 28208 AN: 41412

American (AMR) AF: 0.464 AC: 7075 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1049 AN: 3464

East Asian (EAS) AF: 0.222 AC: 1144 AN: 5154

South Asian (SAS) AF: 0.226 AC: 1085 AN: 4808

European-Finnish (FIN) AF: 0.353 AC: 3699 AN: 10492

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24028 AN: 67906

Other (OTH) AF: 0.415 AC: 876 AN: 2110

Alfa AF: 0.379 Hom.: 13115

Bravo AF: 0.467

Asia WGS AF: 0.247 AC: 857 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.2
DANN	Benign	0.88
PhyloP100		-0.15
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: rs7517826; hg19: chr1-94365334;