chr6-53513279-G-A

Variant names:

• chr6-53513279-G-A
• rs636933
• ENST00000514004.5:c.*919C>T

Variant summary

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

The ENST00000514004.5(GCLC):​c.*919C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,272 control chromosomes in the GnomAD database, including 3,126 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 0.20 (3124 hom., cov: 33)
  • Exomes 𝑓: 0.12 (2 hom.)
• Consequence: GCLC ENST00000514004.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.949
• 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-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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCLC	NM_001498.4	MANE Select	c.753+925C>T		intron	N/A	NP_001489.1
	GCLC	NM_001197115.2		c.639+925C>T		intron	N/A	NP_001184044.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCLC	ENST00000514004.5	TSL:1	c.*919C>T		3_prime_UTR	Exon 6 of 6	ENSP00000421908.1
	GCLC	ENST00000650454.1	MANE Select	c.753+925C>T		intron	N/A	ENSP00000497574.1
	GCLC	ENST00000616923.5	TSL:1	c.594+925C>T		intron	N/A	ENSP00000482756.2

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30385 AN: 152062 Hom.: 3122 Cov.: 33

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.194

GnomAD4 exome AF: 0.120 AC: 11 AN: 92 Hom.: 2 Cov.: 0 AF XY: 0.0625 AC XY: 4 AN XY: 64

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.125 AC: 2 AN: 16

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.155 AC: 9 AN: 58

Other (OTH) AF: 0.00 AC: 0 AN: 8

GnomAD4 genome AF: 0.200 AC: 30384 AN: 152180 Hom.: 3124 Cov.: 33 AF XY: 0.197 AC XY: 14643 AN XY: 74414

African (AFR) AF: 0.168 AC: 6955 AN: 41518

American (AMR) AF: 0.143 AC: 2182 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3470

East Asian (EAS) AF: 0.139 AC: 721 AN: 5180

South Asian (SAS) AF: 0.136 AC: 657 AN: 4826

European-Finnish (FIN) AF: 0.241 AC: 2548 AN: 10588

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.237 AC: 16080 AN: 67980

Other (OTH) AF: 0.194 AC: 410 AN: 2114

Alfa AF: 0.215 Hom.: 1214

Bravo AF: 0.192

Asia WGS AF: 0.129 AC: 450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.65
PhyloP100		-0.95
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: rs636933; hg19: chr6-53378077;