rs2303519

chr8-66456949-C-T

Variant summary

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

The NM_144650.3(ADHFE1):c.1065+54C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,447,430 control chromosomes in the GnomAD database, including 23,266 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 0.20 (3417 hom., cov: 32)
  • Exomes 𝑓: 0.17 (19849 hom.)
• Consequence: ADHFE1 NM_144650.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.500

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADHFE1	NM_144650.3	c.1065+54C>T		intron_variant		ENST00000396623.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADHFE1	ENST00000396623.8	c.1065+54C>T		intron_variant		1	NM_144650.3	P1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30805 AN: 152002 Hom.: 3406 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.196

GnomAD4 exome AF: 0.169 AC: 219062 AN: 1295312 Hom.: 19849 Cov.: 20 AF XY: 0.170 AC XY: 109032 AN XY: 641186

Gnomad4 AFR exome AF: 0.279

Gnomad4 AMR exome AF: 0.324

Gnomad4 ASJ exome AF: 0.108

Gnomad4 EAS exome AF: 0.142

Gnomad4 SAS exome AF: 0.239

Gnomad4 FIN exome AF: 0.152

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.173

GnomAD4 genome AF: 0.203 AC: 30841 AN: 152118 Hom.: 3417 Cov.: 32 AF XY: 0.203 AC XY: 15082 AN XY: 74380

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.201

Alfa AF: 0.173 Hom.: 4984

Bravo AF: 0.214

Asia WGS AF: 0.213 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	2.6
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: rs2303519; hg19: chr8-67369184; COSMIC: COSV52560183; COSMIC: COSV52560183;