6-53499150-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001498.4(GCLC):c.1703-183C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0994 in 152,152 control chromosomes in the GnomAD database, including 1,385 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.099 (1385 hom., cov: 32)
• Consequence: GCLC NM_001498.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.385

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]

GCLC-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-53499150-G-C is Benign according to our data. Variant chr6-53499150-G-C is described in ClinVar as [Benign]. Clinvar id is 1278938.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCLC	NM_001498.4	c.1703-183C>G		intron_variant		ENST00000650454.1
GCLC-AS1	NR_183318.1	n.327-7004G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCLC	ENST00000650454.1	c.1703-183C>G		intron_variant			NM_001498.4	P1

Frequencies

GnomAD3 genomes AF: 0.0992 AC: 15082 AN: 152034 Hom.: 1374 Cov.: 32

Gnomad AFR AF: 0.0918

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.0530

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.0459

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0517

Gnomad OTH AF: 0.0956

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

GnomAD4 genome AF: 0.0994 AC: 15125 AN: 152152 Hom.: 1385 Cov.: 32 AF XY: 0.107 AC XY: 7944 AN XY: 74400

Gnomad4 AFR AF: 0.0918

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.0530

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.0459

Gnomad4 NFE AF: 0.0517

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0690 Hom.: 95

Bravo AF: 0.117

Asia WGS AF: 0.221 AC: 767 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.97
Dann	Benign	0.64

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: rs16883893; hg19: chr6-53363948;