6-53564474-A-G

Position:

• chr6-53564474-A-G

Variant summary

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

The NR_110840.1(KILH):​n.400-54T>C 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 0.146 in 152,206 control chromosomes in the GnomAD database, including 1,697 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 0.15 (1695 hom., cov: 32)
  • Exomes 𝑓: 0.32 (2 hom.)
• Consequence: KILH NR_110840.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.337

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KILH	NR_110840.1	n.400-54T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KILH	ENST00000502390.5	n.522-54T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22195 AN: 152066 Hom.: 1694 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.146

GnomAD4 exome AF: 0.318 AC: 7 AN: 22 Hom.: 2 AF XY: 0.286 AC XY: 4 AN XY: 14

Gnomad4 NFE exome AF: 0.318

GnomAD4 genome AF: 0.146 AC: 22207 AN: 152184 Hom.: 1695 Cov.: 32 AF XY: 0.149 AC XY: 11081 AN XY: 74402

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.145

Alfa AF: 0.143 Hom.: 2251

Bravo AF: 0.141

Asia WGS AF: 0.227 AC: 791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.4
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1883633; hg19: chr6-53429272;