chr1-93887893-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002061.4. 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.*1097C>A		3_prime_UTR	Exon 7 of 7	NP_002052.1
	GCLM	NM_001308253.2		c.*1097C>A		3_prime_UTR	Exon 6 of 6	NP_001295182.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCLM	ENST00000370238.8	TSL:1 MANE Select	c.*1097C>A		3_prime_UTR	Exon 7 of 7	ENSP00000359258.3
	GCLM	ENST00000615724.1	TSL:1	c.*1097C>A		3_prime_UTR	Exon 6 of 6	ENSP00000484507.1
	ENSG00000310419	ENST00000849663.1		n.401+5308G>T		intron	N/A

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.681 AC: 28286 AN: 41510

American (AMR) AF: 0.464 AC: 7093 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1047 AN: 3468

East Asian (EAS) AF: 0.222 AC: 1149 AN: 5172

South Asian (SAS) AF: 0.226 AC: 1090 AN: 4824

European-Finnish (FIN) AF: 0.352 AC: 3710 AN: 10526

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

European-Non Finnish (NFE) AF: 0.354 AC: 24049 AN: 67958

Other (OTH) AF: 0.416 AC: 878 AN: 2110

Alfa AF: 0.404 Hom.: 11409

Bravo AF: 0.467

Asia WGS AF: 0.249 AC: 868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.1
DANN	Benign	0.47
PhyloP100		0.91
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: rs7549683; hg19: chr1-94353449;