6-53583136-T-C

Variant names:

• chr6-53583136-T-C
• rs513041
• ENST00000505995.5:n.110-13531A>G

Variant summary

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

The ENST00000505995.5(KILH):​n.110-13531A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 152,000 control chromosomes in the GnomAD database, including 22,135 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 0.52 (22135 hom., cov: 32)
• Consequence: KILH ENST00000505995.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 6 publications found

Genes affected

KILH (HGNC:56729): (KRT19 interacting long noncoding RNA in hepatocellular carcinoma)

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KILH	ENST00000505995.5	n.110-13531A>G		intron_variant	Intron 1 of 3	1
GCLC	ENST00000505197.1	c.-453-18247A>G		intron_variant	Intron 1 of 3	4		ENSP00000427403.1
KILH	ENST00000502390.5	n.123-9861A>G		intron_variant	Intron 1 of 4	2

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78928 AN: 151880 Hom.: 22082 Cov.: 32

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.520 AC: 79039 AN: 152000 Hom.: 22135 Cov.: 32 AF XY: 0.523 AC XY: 38855 AN XY: 74302

African (AFR) AF: 0.727 AC: 30144 AN: 41458

American (AMR) AF: 0.430 AC: 6573 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1339 AN: 3472

East Asian (EAS) AF: 0.743 AC: 3841 AN: 5168

South Asian (SAS) AF: 0.608 AC: 2925 AN: 4814

European-Finnish (FIN) AF: 0.455 AC: 4797 AN: 10546

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.412 AC: 27981 AN: 67952

Other (OTH) AF: 0.480 AC: 1015 AN: 2114

Alfa AF: 0.452 Hom.: 41729

Bravo AF: 0.525

Asia WGS AF: 0.701 AC: 2436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.15
DANN	Benign	0.50
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs513041; hg19: chr6-53447934;