rs553822

Positions:

• chr6-53515915-C-T

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.560+194G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 151,976 control chromosomes in the GnomAD database, including 33,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.65 (33337 hom., cov: 31)
• Consequence: GCLC NM_001498.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.737

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-53515915-C-T is Benign according to our data. Variant chr6-53515915-C-T is described in ClinVar as [Benign]. Clinvar id is 1265435.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCLC	NM_001498.4	c.560+194G>A		intron_variant		ENST00000650454.1	NP_001489.1
GCLC	NM_001197115.2	c.447-1418G>A		intron_variant			NP_001184044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCLC	ENST00000650454.1	c.560+194G>A		intron_variant			NM_001498.4	ENSP00000497574	P1

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99415 AN: 151858 Hom.: 33281 Cov.: 31

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.655 AC: 99528 AN: 151976 Hom.: 33337 Cov.: 31 AF XY: 0.659 AC XY: 48972 AN XY: 74302

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.682

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.711

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.611

Alfa AF: 0.593 Hom.: 26422

Bravo AF: 0.662

Asia WGS AF: 0.702 AC: 2441 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	-0.91
CADD	Benign	0.29
DANN	Benign	0.71

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: rs553822; hg19: chr6-53380713;