Variant 6-53498978-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001498.4(GCLC):c.1703-11C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00234 in 1,581,032 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 97 hom. )

Consequence

GCLC
NM_001498.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0002752

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.02

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:):

GCLC-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 6-53498978-G-C is Benign according to our data. Variant chr6-53498978-G-C is described in ClinVar as [Benign]. Clinvar id is 811041.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0586 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.1703-11C>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000650454.1	NP_001489.1
GCLC-AS1	NR_183318.1 linkuse as main transcript	n.327-7176G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCLC	ENST00000650454.1 linkuse as main transcript	c.1703-11C>G		splice_polypyrimidine_tract_variant, intron_variant			NM_001498.4	ENSP00000497574	P1

Frequencies

GnomAD3 genomes

AF:

0.00272

AC:

411

AN:

151226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000535

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.0641

Gnomad SAS

AF:

0.00209

Gnomad FIN

AF:

0.0000972

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000295

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.00603

AC:

1478

AN:

245266

Hom.:

AF XY:

0.00554

AC XY:

735

AN XY:

132656

show subpopulations

Gnomad AFR exome

AF:

0.000868

Gnomad AMR exome

AF:

0.000204

Gnomad ASJ exome

AF:

0.000807

Gnomad EAS exome

AF:

0.0741

Gnomad SAS exome

AF:

0.00191

Gnomad FIN exome

AF:

0.0000466

Gnomad NFE exome

AF:

0.000256

Gnomad OTH exome

AF:

0.00183

GnomAD4 exome

AF:

0.00230

AC:

3292

AN:

1429688

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

1613

AN XY:

712754

show subpopulations

Gnomad4 AFR exome

AF:

0.000367

Gnomad4 AMR exome

AF:

0.000225

Gnomad4 ASJ exome

AF:

0.000775

Gnomad4 EAS exome

AF:

0.0638

Gnomad4 SAS exome

AF:

0.00191

Gnomad4 FIN exome

AF:

0.000356

Gnomad4 NFE exome

AF:

0.000237

Gnomad4 OTH exome

AF:

0.00483

GnomAD4 genome

AF:

0.00272

AC:

411

AN:

151344

Hom.:

Cov.:

AF XY:

0.00286

AC XY:

211

AN XY:

73888

show subpopulations

Gnomad4 AFR

AF:

0.000533

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.0643

Gnomad4 SAS

AF:

0.00209

Gnomad4 FIN

AF:

0.0000972

Gnomad4 NFE

AF:

0.000295

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.000898

Hom.:

Bravo

AF:

0.00321

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Apr 14, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.021

DANN

Benign

0.32

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00028

dbscSNV1_RF

Benign

0.040

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