1-93887893-G-T

Variant names:

• chr1-93887893-G-T
• rs7549683
• NM_002061.4:c.*1097C>A

Variant summary

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

The NM_002061.4(GCLM):​c.*1097C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,046 control chromosomes in the GnomAD database, including 16,932 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 0.45 (16932 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: GCLM NM_002061.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.911

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCLM	NM_002061.4	c.*1097C>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000370238.8	NP_002052.1
GCLM	NM_001308253.2	c.*1097C>A		3_prime_UTR_variant	Exon 6 of 6		NP_001295182.1
GCLM	XM_011541261.3	c.*1097C>A		3_prime_UTR_variant	Exon 7 of 7		XP_011539563.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCLM	ENST00000370238	c.*1097C>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_002061.4	ENSP00000359258.3
GCLM	ENST00000615724	c.*1097C>A		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000484507.1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67592 AN: 151928 Hom.: 16897 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.416

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.445 AC: 67684 AN: 152046 Hom.: 16932 Cov.: 32 AF XY: 0.442 AC XY: 32877 AN XY: 74302

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.416

Alfa AF: 0.360 Hom.: 4361

Bravo AF: 0.467

Asia WGS AF: 0.249 AC: 868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.1
DANN	Benign	0.47

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: rs7549683; hg19: chr1-94353449;