rs890515

Variant names:

• chr8-66459599-T-A
• rs890515
• NM_144650.3:c.1163-709T>A

Your query was ambiguous. Multiple possible variants found:

• chr8-66459599-T-A
• chr8-66459599-T-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.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
• 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=-0.89).
• 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 rank	MANE	Protein	UniProt
ADHFE1	NM_144650.3	c.1163-709T>A		intron_variant	Intron 12 of 13	ENST00000396623.8	NP_653251.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADHFE1	ENST00000396623.8	c.1163-709T>A		intron_variant	Intron 12 of 13	1	NM_144650.3	ENSP00000379865.3
ENSG00000285791	ENST00000648156.1	n.*382-709T>A		intron_variant	Intron 11 of 19			ENSP00000497007.1

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

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: 0.750 AC: 3 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.828 AC: 34204 AN: 41326

American (AMR) AF: 0.704 AC: 10724 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1775 AN: 3462

East Asian (EAS) AF: 0.593 AC: 3051 AN: 5142

South Asian (SAS) AF: 0.639 AC: 3069 AN: 4804

European-Finnish (FIN) AF: 0.586 AC: 6081 AN: 10380

Middle Eastern (MID) AF: 0.664 AC: 194 AN: 292

European-Non Finnish (NFE) AF: 0.523 AC: 35455 AN: 67844

Other (OTH) AF: 0.640 AC: 1336 AN: 2088

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
PhyloP100		-1.1
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: rs890515; hg19: chr8-67371834;