21-44478486-T-G

Variant names:

• chr21-44478486-T-G
• rs2838571
• ENST00000617205.2:n.1385T>G

Variant summary

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

The ENST00000617205.2(HEPFAL):​n.1385T>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 ENST00000617205.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• Publications: 6 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HEPFAL	XR_007067903.1	n.3596T>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEPFAL	ENST00000617205.2	n.1385T>G		non_coding_transcript_exon_variant	Exon 2 of 2	6

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.450 AC: 9 AN: 20

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.193 AC: 8009 AN: 41536

American (AMR) AF: 0.442 AC: 6767 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1436 AN: 3470

East Asian (EAS) AF: 0.479 AC: 2474 AN: 5170

South Asian (SAS) AF: 0.492 AC: 2377 AN: 4830

European-Finnish (FIN) AF: 0.511 AC: 5399 AN: 10572

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32884 AN: 67978

Other (OTH) AF: 0.419 AC: 886 AN: 2116

Alfa AF: 0.413 Hom.: 2331

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
PhyloP100		0.13

Splicing

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

Other links and lift over

dbSNP: rs2838571; hg19: chr21-45898369;