rs2303519

Variant names:

• chr8-66456949-C-T
• rs2303519
• NM_144650.3:c.1065+54C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-0.79).
• 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 rank	MANE	Protein	UniProt
ADHFE1	NM_144650.3	c.1065+54C>T		intron_variant	Intron 11 of 13	ENST00000396623.8	NP_653251.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADHFE1	ENST00000396623.8	c.1065+54C>T		intron_variant	Intron 11 of 13	1	NM_144650.3	ENSP00000379865.3
ENSG00000285791	ENST00000648156.1	n.*284+54C>T		intron_variant	Intron 10 of 19			ENSP00000497007.1

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

African (AFR) AF: 0.279 AC: 7813 AN: 27992

American (AMR) AF: 0.324 AC: 9043 AN: 27916

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 2206 AN: 20346

East Asian (EAS) AF: 0.142 AC: 5291 AN: 37390

South Asian (SAS) AF: 0.239 AC: 14838 AN: 62198

European-Finnish (FIN) AF: 0.152 AC: 7429 AN: 48896

Middle Eastern (MID) AF: 0.209 AC: 801 AN: 3840

European-Non Finnish (NFE) AF: 0.160 AC: 162392 AN: 1013208

Other (OTH) AF: 0.173 AC: 9249 AN: 53526

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

African (AFR) AF: 0.269 AC: 11161 AN: 41470

American (AMR) AF: 0.276 AC: 4227 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3464

East Asian (EAS) AF: 0.155 AC: 801 AN: 5178

South Asian (SAS) AF: 0.236 AC: 1136 AN: 4816

European-Finnish (FIN) AF: 0.139 AC: 1472 AN: 10596

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.163 AC: 11056 AN: 67994

Other (OTH) AF: 0.201 AC: 424 AN: 2110

Alfa AF: 0.177 Hom.: 10812

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
PhyloP100		-0.50
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: rs2303519; hg19: chr8-67369184; COSMIC: COSV52560183; COSMIC: COSV52560183;