ENST00000514004:c.*1162G>A

Variant names:

• chr6-53513036-C-T
• rs574389
• ENST00000514004.5:c.*1162G>A

Variant summary

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

The ENST00000514004.5(GCLC):​c.*1162G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 152,078 control chromosomes in the GnomAD database, including 15,380 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 0.44 (15380 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: GCLC ENST00000514004.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 16 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000514004.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCLC	NM_001498.4	MANE Select	c.753+1168G>A		intron	N/A	NP_001489.1	P48506
	GCLC	NM_001197115.2		c.639+1168G>A		intron	N/A	NP_001184044.1	E1CEI4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCLC	ENST00000514004.5	TSL:1	c.*1162G>A		3_prime_UTR	Exon 6 of 6	ENSP00000421908.1	A0A0C4DGB2
	GCLC	ENST00000650454.1	MANE Select	c.753+1168G>A		intron	N/A	ENSP00000497574.1	P48506
	GCLC	ENST00000616923.5	TSL:1	c.594+1168G>A		intron	N/A	ENSP00000482756.2	B4E2I4

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67457 AN: 151960 Hom.: 15367 Cov.: 33

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.452

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

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.444 AC: 67492 AN: 152078 Hom.: 15380 Cov.: 33 AF XY: 0.447 AC XY: 33219 AN XY: 74340

African (AFR) AF: 0.359 AC: 14912 AN: 41482

American (AMR) AF: 0.570 AC: 8705 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1362 AN: 3470

East Asian (EAS) AF: 0.404 AC: 2093 AN: 5182

South Asian (SAS) AF: 0.523 AC: 2520 AN: 4820

European-Finnish (FIN) AF: 0.452 AC: 4776 AN: 10558

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.465 AC: 31627 AN: 67978

Other (OTH) AF: 0.456 AC: 962 AN: 2110

Alfa AF: 0.462 Hom.: 52682

Bravo AF: 0.448

Asia WGS AF: 0.464 AC: 1615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.53
PhyloP100		-0.069
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: rs574389; hg19: chr6-53377834;