rs6933870

Positions:

• chr6-53533172-C-G
• chr6-53533172-C-T

Variant summary

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

The NM_001498.4(GCLC):​c.151-10645G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 152,054 control chromosomes in the GnomAD database, including 18,113 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 0.49 (18113 hom., cov: 32)
• Consequence: GCLC NM_001498.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCLC	NM_001498.4	c.151-10645G>C		intron_variant		ENST00000650454.1	NP_001489.1
GCLC	NM_001197115.2	c.151-10645G>C		intron_variant			NP_001184044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCLC	ENST00000650454.1	c.151-10645G>C		intron_variant			NM_001498.4	ENSP00000497574	P1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73859 AN: 151936 Hom.: 18091 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.486 AC: 73927 AN: 152054 Hom.: 18113 Cov.: 32 AF XY: 0.489 AC XY: 36363 AN XY: 74354

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.489

Alfa AF: 0.462 Hom.: 1951

Bravo AF: 0.497

Asia WGS AF: 0.474 AC: 1648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.39

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: rs6933870; hg19: chr6-53397970;