chr6-53499011-GT-G

Variant names:

• chr6-53499011-GT-G
• rs17880610
• NM_001498.4:c.1703-45delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001498.4(GCLC):​c.1703-45delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,104,738 control chromosomes in the GnomAD database, including 6,093 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (966 hom., cov: 30)
  • Exomes 𝑓: 0.10 (5127 hom.)
• Consequence: GCLC NM_001498.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0660
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 6-53499011-GT-G is Benign according to our data. Variant chr6-53499011-GT-G is described in ClinVar as Benign. ClinVar VariationId is 1278849.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.14 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCLC	NM_001498.4	MANE Select	c.1703-45delA		intron	N/A	NP_001489.1	P48506
	GCLC	NM_001197115.2		c.1589-45delA		intron	N/A	NP_001184044.1	E1CEI4
	GCLC-AS1	NR_183318.1		n.327-7133delT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCLC	ENST00000650454.1	MANE Select	c.1703-45delA		intron	N/A	ENSP00000497574.1	P48506
	GCLC	ENST00000616923.5	TSL:1	c.1544-45delA		intron	N/A	ENSP00000482756.2	B4E2I4
	GCLC	ENST00000515580.1	TSL:1	n.1307-45delA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16757 AN: 149634 Hom.: 964 Cov.: 30

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0844

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.00838

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0897

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.115

GnomAD2 exomes AF: 0.135 AC: 23961 AN: 177400 AF XY: 0.141

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.0778

Gnomad ASJ exome AF: 0.159

Gnomad EAS exome AF: 0.0131

Gnomad FIN exome AF: 0.172

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.148

GnomAD4 exome AF: 0.102 AC: 97017 AN: 955004 Hom.: 5127 Cov.: 12 AF XY: 0.105 AC XY: 51815 AN XY: 492614

African (AFR) AF: 0.129 AC: 2957 AN: 22956

American (AMR) AF: 0.0615 AC: 2406 AN: 39130

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 2510 AN: 21220

East Asian (EAS) AF: 0.00612 AC: 203 AN: 33156

South Asian (SAS) AF: 0.155 AC: 10973 AN: 70752

European-Finnish (FIN) AF: 0.141 AC: 6830 AN: 48586

Middle Eastern (MID) AF: 0.105 AC: 489 AN: 4646

European-Non Finnish (NFE) AF: 0.0983 AC: 66046 AN: 672156

Other (OTH) AF: 0.109 AC: 4603 AN: 42402

GnomAD4 genome AF: 0.112 AC: 16760 AN: 149734 Hom.: 966 Cov.: 30 AF XY: 0.112 AC XY: 8206 AN XY: 72980

African (AFR) AF: 0.133 AC: 5409 AN: 40802

American (AMR) AF: 0.0843 AC: 1267 AN: 15034

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 362 AN: 3442

East Asian (EAS) AF: 0.00840 AC: 43 AN: 5120

South Asian (SAS) AF: 0.149 AC: 701 AN: 4704

European-Finnish (FIN) AF: 0.142 AC: 1436 AN: 10128

Middle Eastern (MID) AF: 0.0972 AC: 28 AN: 288

European-Non Finnish (NFE) AF: 0.107 AC: 7163 AN: 67238

Other (OTH) AF: 0.114 AC: 237 AN: 2072

Alfa AF: 0.0712 Hom.: 107

Bravo AF: 0.106

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.066
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: rs17880610; hg19: chr6-53363809; COSMIC: COSV57593542; COSMIC: COSV57593542;