rs890515

chr8-66459599-T-Achr8-66459599-T-G

Variant summary

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

The NM_144650.3(ADHFE1):c.1163-709T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 151,478 control chromosomes in the GnomAD database, including 32,017 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 0.64 (32016 hom., cov: 28)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: ADHFE1 NM_144650.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

Genes affected

ADHFE1 (HGNC:16354): (alcohol dehydrogenase iron containing 1) The ADHFE1 gene encodes hydroxyacid-oxoacid transhydrogenase (EC 1.1.99.24), which is responsible for the oxidation of 4-hydroxybutyrate in mammalian tissues (Kardon et al., 2006 [PubMed 16616524]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADHFE1	NM_144650.3	c.1163-709T>A		intron_variant		ENST00000396623.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADHFE1	ENST00000396623.8	c.1163-709T>A		intron_variant		1	NM_144650.3	P1

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96154 AN: 151360 Hom.: 31960 Cov.: 28

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.639

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.636 AC: 96271 AN: 151472 Hom.: 32016 Cov.: 28 AF XY: 0.640 AC XY: 47337 AN XY: 74008

Gnomad4 AFR AF: 0.828

Gnomad4 AMR AF: 0.704

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.640

Alfa AF: 0.578 Hom.: 3320

Bravo AF: 0.652

Asia WGS AF: 0.632 AC: 2198 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.99
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs890515; hg19: chr8-67371834;