Variant 6-53505309-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001498.4(GCLC):c.1395+83A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 727,974 control chromosomes in the GnomAD database, including 90,284 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.53 ( 22331 hom., cov: 31)

Exomes 𝑓: 0.48 ( 67953 hom. )

Consequence

GCLC
NM_001498.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.332

Variant links:

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 links:

GCLC (HGNC:):

GCLC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 6-53505309-T-C is Benign according to our data. Variant chr6-53505309-T-C is described in ClinVar as [Benign]. Clinvar id is 1289924.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-53505309-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCLC	NM_001498.4 linkuse as main transcript	c.1395+83A>G		intron_variant		ENST00000650454.1	NP_001489.1	P48506Q14TF0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCLC	ENST00000650454.1 linkuse as main transcript	c.1395+83A>G		intron_variant			NM_001498.4	ENSP00000497574.1		P48506

Frequencies

GnomAD3 genomes

AF:

0.528

AC:

80094

AN:

151684

Hom.:

22297

Cov.:

show subpopulations

Gnomad AFR

AF:

0.685

Gnomad AMI

AF:

0.400

Gnomad AMR

AF:

0.605

Gnomad ASJ

AF:

0.400

Gnomad EAS

AF:

0.593

Gnomad SAS

AF:

0.530

Gnomad FIN

AF:

0.473

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.428

Gnomad OTH

AF:

0.501

GnomAD3 exomes

AF:

0.513

AC:

76977

AN:

150098

Hom.:

20549

AF XY:

0.504

AC XY:

40063

AN XY:

79548

show subpopulations

Gnomad AFR exome

AF:

0.689

Gnomad AMR exome

AF:

0.679

Gnomad ASJ exome

AF:

0.419

Gnomad EAS exome

AF:

0.586

Gnomad SAS exome

AF:

0.517

Gnomad FIN exome

AF:

0.469

Gnomad NFE exome

AF:

0.431

Gnomad OTH exome

AF:

0.492

GnomAD4 exome

AF:

0.477

AC:

274928

AN:

576168

Hom.:

67953

Cov.:

AF XY:

0.476

AC XY:

147647

AN XY:

310046

show subpopulations

Gnomad4 AFR exome

AF:

0.686

Gnomad4 AMR exome

AF:

0.668

Gnomad4 ASJ exome

AF:

0.417

Gnomad4 EAS exome

AF:

0.637

Gnomad4 SAS exome

AF:

0.520

Gnomad4 FIN exome

AF:

0.467

Gnomad4 NFE exome

AF:

0.429

Gnomad4 OTH exome

AF:

0.482

GnomAD4 genome

AF:

0.528

AC:

80194

AN:

151806

Hom.:

22331

Cov.:

AF XY:

0.533

AC XY:

39516

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.685

Gnomad4 AMR

AF:

0.605

Gnomad4 ASJ

AF:

0.400

Gnomad4 EAS

AF:

0.594

Gnomad4 SAS

AF:

0.530

Gnomad4 FIN

AF:

0.473

Gnomad4 NFE

AF:

0.428

Gnomad4 OTH

AF:

0.505

Alfa

AF:

0.463

Hom.:

4666

Bravo

AF:

0.546

Asia WGS

AF:

0.558

AC:

1938

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.4

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over