chr6-53497649-G-GAA

Variant names:

• chr6-53497649-G-GAA
• rs3830796
• NM_001498.4:c.*1105_*1106dupTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001498.4(GCLC):​c.*1105_*1106dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.015 (53 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GCLC NM_001498.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.813
• Publications: 5 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0151 (2290/151572) while in subpopulation AFR AF = 0.0514 (2122/41306). AF 95% confidence interval is 0.0496. There are 53 homozygotes in GnomAd4. There are 1057 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 53 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCLC	NM_001498.4	c.*1105_*1106dupTT		3_prime_UTR_variant	Exon 16 of 16	ENST00000650454.1	NP_001489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCLC	ENST00000650454.1	c.*1105_*1106dupTT		3_prime_UTR_variant	Exon 16 of 16		NM_001498.4	ENSP00000497574.1

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2277 AN: 151460 Hom.: 53 Cov.: 0

Gnomad AFR AF: 0.0512

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00579

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000624

Gnomad FIN AF: 0.0000956

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000752

Gnomad OTH AF: 0.0115

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 432 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0151 AC: 2290 AN: 151572 Hom.: 53 Cov.: 0 AF XY: 0.0143 AC XY: 1057 AN XY: 74008

African (AFR) AF: 0.0514 AC: 2122 AN: 41306

American (AMR) AF: 0.00578 AC: 88 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000625 AC: 3 AN: 4802

European-Finnish (FIN) AF: 0.0000956 AC: 1 AN: 10456

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000752 AC: 51 AN: 67854

Other (OTH) AF: 0.0114 AC: 24 AN: 2100

Alfa AF: 0.00 Hom.: 188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3830796; hg19: chr6-53362447;