Variant 6-53505597-C-T 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.1291-101G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 771,814 control chromosomes in the GnomAD database, including 17,954 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.20 ( 3053 hom., cov: 31)

Exomes 𝑓: 0.21 ( 14901 hom. )

Consequence

GCLC
NM_001498.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.283

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-AS1 (HGNC:56649): (GCLC antisense RNA 1)

GCLC-AS1 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=-0.82).

BP6

Variant 6-53505597-C-T is Benign according to our data. Variant chr6-53505597-C-T is described in ClinVar as [Benign]. Clinvar id is 1235148.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCLC	NM_001498.4 linkuse as main transcript	c.1291-101G>A		intron_variant		ENST00000650454.1
GCLC-AS1	NR_183318.1 linkuse as main transcript	n.327-557C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCLC	ENST00000650454.1 linkuse as main transcript	c.1291-101G>A		intron_variant			NM_001498.4	P1
GCLC-AS1	ENST00000655377.1 linkuse as main transcript	n.212-557C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

29691

AN:

151906

Hom.:

3053

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.185

Gnomad EAS

AF:

0.132

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.173

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.189

GnomAD4 exome

AF:

0.214

AC:

132420

AN:

619790

Hom.:

14901

Cov.:

AF XY:

0.211

AC XY:

70441

AN XY:

333058

show subpopulations

Gnomad4 AFR exome

AF:

0.139

Gnomad4 AMR exome

AF:

0.112

Gnomad4 ASJ exome

AF:

0.186

Gnomad4 EAS exome

AF:

0.168

Gnomad4 SAS exome

AF:

0.143

Gnomad4 FIN exome

AF:

0.232

Gnomad4 NFE exome

AF:

0.244

Gnomad4 OTH exome

AF:

0.205

GnomAD4 genome

AF:

0.195

AC:

29690

AN:

152024

Hom.:

3053

Cov.:

AF XY:

0.192

AC XY:

14275

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.146

Gnomad4 AMR

AF:

0.143

Gnomad4 ASJ

AF:

0.185

Gnomad4 EAS

AF:

0.133

Gnomad4 SAS

AF:

0.132

Gnomad4 FIN

AF:

0.232

Gnomad4 NFE

AF:

0.242

Gnomad4 OTH

AF:

0.190

Alfa

AF:

0.226

Hom.:

6656

Bravo

AF:

0.187

Asia WGS

AF:

0.130

AC:

452

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

-0.82

CADD

Benign

6.3

DANN

Benign

0.55

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