rs2465983

Variant names:

• chr8-66451377-A-G
• rs2465983
• NM_144650.3:c.735-576A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

ENSG00000285791 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144650.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADHFE1	NM_144650.3	MANE Select	c.735-576A>G		intron	N/A	NP_653251.2	Q8IWW8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADHFE1	ENST00000396623.8	TSL:1 MANE Select	c.735-576A>G		intron	N/A	ENSP00000379865.3	Q8IWW8-1
	ADHFE1	ENST00000424777.6	TSL:1	n.735-576A>G		intron	N/A	ENSP00000410883.2	Q8IWW8-3
	ADHFE1	ENST00000426810.5	TSL:1	n.*571-576A>G		intron	N/A	ENSP00000406905.1	F2Z3E5

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

African (AFR) AF: 0.132 AC: 5473 AN: 41536

American (AMR) AF: 0.145 AC: 2224 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 560 AN: 3468

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5192

South Asian (SAS) AF: 0.0987 AC: 476 AN: 4824

European-Finnish (FIN) AF: 0.195 AC: 2065 AN: 10596

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 13005 AN: 67998

Other (OTH) AF: 0.181 AC: 382 AN: 2112

Alfa AF: 0.184 Hom.: 3389

Bravo AF: 0.156

Asia WGS AF: 0.0520 AC: 181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.49
DANN	Benign	0.50
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2465983; hg19: chr8-67363612;