6-53583136-T-C

Position:

• chr6-53583136-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000502390.5(KILH):​n.123-9861A>G variant causes a intron, non coding transcript 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 ENST00000502390.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KILH	ENST00000502390.5	n.123-9861A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.727

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.743

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.480

Alfa AF: 0.430 Hom.: 23112

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs513041; hg19: chr6-53447934;