chr6-53515915-C-T

Variant names:

• chr6-53515915-C-T
• rs553822
• NM_001498.4:c.560+194G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.737
• Publications: 9 publications found

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001498.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCLC	NM_001498.4	MANE Select	c.560+194G>A		intron	N/A	NP_001489.1
	GCLC	NM_001197115.2		c.447-1418G>A		intron	N/A	NP_001184044.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCLC	ENST00000650454.1	MANE Select	c.560+194G>A		intron	N/A	ENSP00000497574.1
	GCLC	ENST00000616923.5	TSL:1	c.401+194G>A		intron	N/A	ENSP00000482756.2
	GCLC	ENST00000514004.5	TSL:1	c.560+194G>A		intron	N/A	ENSP00000421908.1

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99415 AN: 151858 Hom.: 33281 Cov.: 31

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.: 31 AF XY: 0.659 AC XY: 48972 AN XY: 74302

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

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.29
DANN	Benign	0.71
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs553822; hg19: chr6-53380713;