dbSNP rs553822: GCLC:c.560+194G>A (chr6-53515915-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.737

Publications

9 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
GCLC	NM_001498.4 link	c.560+194G>A		intron_variant	Intron 4 of 15	ENST00000650454.1	NP_001489.1
GCLC	NM_001197115.2 link	c.447-1418G>A		intron_variant	Intron 3 of 14		NP_001184044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCLC	ENST00000650454.1 link	c.560+194G>A		intron_variant	Intron 4 of 15		NM_001498.4	ENSP00000497574.1

Frequencies

GnomAD3 genomes

AF:

0.655

AC:

99415

AN:

151858

Hom.:

33281

Cov.:

show subpopulations

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.:

AF XY:

0.659

AC XY:

48972

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.786

AC:

32613

AN:

41472

American (AMR)

AF:

0.682

AC:

10425

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

1731

AN:

3460

East Asian (EAS)

AF:

0.658

AC:

3401

AN:

5168

South Asian (SAS)

AF:

0.711

AC:

3422

AN:

4810

European-Finnish (FIN)

AF:

0.650

AC:

6847

AN:

10538

Middle Eastern (MID)

AF:

0.582

AC:

171

AN:

294

European-Non Finnish (NFE)

AF:

0.576

AC:

39163

AN:

67938

Other (OTH)

AF:

0.611

AC:

1290

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1719

3438

5158

6877

8596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

800

1600

2400

3200

4000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.606

Hom.:

42805

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

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 18, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.29

(source)

DANN

Benign

0.71

PhyloP100

-0.74

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over