chr21-44478486-T-G

Position:

• chr21-44478486-T-G

Variant summary

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

The ENST00000617205.1(HEPFAL):​n.637T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,194 control chromosomes in the GnomAD database, including 13,407 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 0.40 (13405 hom., cov: 33)
  • Exomes 𝑓: 0.41 (2 hom.)
• Consequence: HEPFAL ENST00000617205.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134

Genes affected

HEPFAL (HGNC:56244): (hepatocellular carcinoma ferroptosis associative lncRNA)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HEPFAL	XR_007067903.1	n.3596T>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEPFAL	ENST00000617205.1	n.637T>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60700 AN: 152052 Hom.: 13404 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.418

GnomAD4 exome AF: 0.409 AC: 9 AN: 22 Hom.: 2 Cov.: 0 AF XY: 0.333 AC XY: 4 AN XY: 12

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.450

GnomAD4 genome AF: 0.399 AC: 60718 AN: 152172 Hom.: 13405 Cov.: 33 AF XY: 0.405 AC XY: 30097 AN XY: 74374

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.479

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.419

Alfa AF: 0.421 Hom.: 2316

Bravo AF: 0.385

Asia WGS AF: 0.460 AC: 1600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.0
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2838571; hg19: chr21-45898369;