rs2465983

Positions:

• chr8-66451377-A-G

Variant summary

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

The NM_144650.3(ADHFE1):​c.735-576A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,222 control chromosomes in the GnomAD database, including 2,111 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 0.16 (2111 hom., cov: 32)
• Consequence: ADHFE1 NM_144650.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.783

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADHFE1	NM_144650.3	c.735-576A>G		intron_variant		ENST00000396623.8	NP_653251.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADHFE1	ENST00000396623.8	c.735-576A>G		intron_variant		1	NM_144650.3	ENSP00000379865	P1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24346 AN: 152104 Hom.: 2109 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0994

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.183

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.160 AC: 24362 AN: 152222 Hom.: 2111 Cov.: 32 AF XY: 0.157 AC XY: 11719 AN XY: 74432

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0987

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.181

Alfa AF: 0.186 Hom.: 2637

Bravo AF: 0.156

Asia WGS AF: 0.0520 AC: 181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.49
DANN	Benign	0.50

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: rs2465983; hg19: chr8-67363612;