rs7758764

Variant names:

• chr6-53531364-G-A
• rs7758764
• NM_001498.4:c.151-8837C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-53531364-G-A
• chr6-53531364-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001498.4(GCLC):​c.151-8837C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,070 control chromosomes in the GnomAD database, including 3,109 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (3109 hom., cov: 32)
• Consequence: GCLC NM_001498.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 7 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 Gene-Disease associations (from GenCC):

• gamma-glutamylcysteine synthetase deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCLC	NM_001498.4	c.151-8837C>T		intron_variant	Intron 1 of 15	ENST00000650454.1	NP_001489.1
GCLC	NM_001197115.2	c.151-8837C>T		intron_variant	Intron 1 of 14		NP_001184044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCLC	ENST00000650454.1	c.151-8837C>T		intron_variant	Intron 1 of 15		NM_001498.4	ENSP00000497574.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25174 AN: 151952 Hom.: 3096 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.0843

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.0456

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.0717

Gnomad OTH AF: 0.165

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.166 AC: 25241 AN: 152070 Hom.: 3109 Cov.: 32 AF XY: 0.171 AC XY: 12684 AN XY: 74360

African (AFR) AF: 0.281 AC: 11641 AN: 41420

American (AMR) AF: 0.331 AC: 5061 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0843 AC: 292 AN: 3462

East Asian (EAS) AF: 0.251 AC: 1298 AN: 5178

South Asian (SAS) AF: 0.223 AC: 1076 AN: 4816

European-Finnish (FIN) AF: 0.0456 AC: 484 AN: 10608

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.0717 AC: 4875 AN: 67996

Other (OTH) AF: 0.169 AC: 357 AN: 2112

Alfa AF: 0.102 Hom.: 597

Bravo AF: 0.193

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.20
DANN	Benign	0.54
PhyloP100		-1.2
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: rs7758764; hg19: chr6-53396162;