rs2397147

Positions:

• chr6-53536789-T-C

Variant summary

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

The NM_001498.4(GCLC):​c.150+7707A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,120 control chromosomes in the GnomAD database, including 8,333 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 0.32 (8333 hom., cov: 33)
• Consequence: GCLC NM_001498.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

Genes affected

GCLC (HGNC:4311): (glutamate-cysteine ligase catalytic 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. This locus encodes the catalytic subunit, while the regulatory subunit is derived from a different gene located on chromosome 1p22-p21. Mutations at this locus have been associated with hemolytic anemia due to deficiency of gamma-glutamylcysteine synthetase and susceptibility to myocardial infarction.[provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCLC	NM_001498.4	c.150+7707A>G		intron_variant		ENST00000650454.1	NP_001489.1
GCLC	NM_001197115.2	c.150+7707A>G		intron_variant			NP_001184044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCLC	ENST00000650454.1	c.150+7707A>G		intron_variant			NM_001498.4	ENSP00000497574	P1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48631 AN: 152002 Hom.: 8336 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.320 AC: 48625 AN: 152120 Hom.: 8333 Cov.: 33 AF XY: 0.318 AC XY: 23640 AN XY: 74360

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.319

Alfa AF: 0.374 Hom.: 18521

Bravo AF: 0.303

Asia WGS AF: 0.241 AC: 840 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.10
DANN	Benign	0.67

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: rs2397147; hg19: chr6-53401587;