Variant 6-53520677-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.446+101G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 917,964 control chromosomes in the GnomAD database, including 44,765 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.28 ( 6536 hom., cov: 32)

Exomes 𝑓: 0.31 ( 38229 hom. )

Consequence

GCLC
NM_001498.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.449

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 6-53520677-C-T is Benign according to our data. Variant chr6-53520677-C-T is described in ClinVar as [Benign]. Clinvar id is 1241264.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.417 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.446+101G>A		intron_variant		ENST00000650454.1	NP_001489.1	P48506Q14TF0
GCLC	NM_001197115.2 linkuse as main transcript	c.446+101G>A		intron_variant			NP_001184044.1	P48506Q14TF0E1CEI4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCLC	ENST00000650454.1 linkuse as main transcript	c.446+101G>A		intron_variant			NM_001498.4	ENSP00000497574.1		P48506

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

43168

AN:

151984

Hom.:

6517

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.272

Gnomad AMR

AF:

0.425

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.384

Gnomad SAS

AF:

0.347

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.282

Gnomad OTH

AF:

0.278

GnomAD4 exome

AF:

0.306

AC:

234195

AN:

765862

Hom.:

38229

AF XY:

0.305

AC XY:

124899

AN XY:

408940

show subpopulations

Gnomad4 AFR exome

AF:

0.213

Gnomad4 AMR exome

AF:

0.527

Gnomad4 ASJ exome

AF:

0.247

Gnomad4 EAS exome

AF:

0.420

Gnomad4 SAS exome

AF:

0.338

Gnomad4 FIN exome

AF:

0.281

Gnomad4 NFE exome

AF:

0.283

Gnomad4 OTH exome

AF:

0.291

GnomAD4 genome

AF:

0.284

AC:

43215

AN:

152102

Hom.:

6536

Cov.:

AF XY:

0.288

AC XY:

21429

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.221

Gnomad4 AMR

AF:

0.426

Gnomad4 ASJ

AF:

0.236

Gnomad4 EAS

AF:

0.385

Gnomad4 SAS

AF:

0.348

Gnomad4 FIN

AF:

0.280

Gnomad4 NFE

AF:

0.282

Gnomad4 OTH

AF:

0.284

Alfa

AF:

0.292

Hom.:

6788

Bravo

AF:

0.294

Asia WGS

AF:

0.340

AC:

1183

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

-0.91

CADD

Benign

0.17

DANN

Benign

0.62

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