dbSNP rs2303519: ADHFE1:c.1065+54C>T (chr8-66456949-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.500

Publications

11 publications found

Variant links:

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]

ADHFE1 links:

ENSG00000285791 (HGNC:):

ENSG00000285791 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

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.1065+54C>T		intron	N/A	NP_653251.2	Q8IWW8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADHFE1	ENST00000396623.8	TSL:1 MANE Select	c.1065+54C>T	intron	N/A	ENSP00000379865.3	Q8IWW8-1
ADHFE1	ENST00000424777.6	TSL:1	n.*502+54C>T	intron	N/A	ENSP00000410883.2	Q8IWW8-3
ADHFE1	ENST00000426810.5	TSL:1	n.*1250+54C>T	intron	N/A	ENSP00000406905.1	F2Z3E5

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30805

AN:

152002

Hom.:

3406

Cov.:

show subpopulations

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.:

AF XY:

0.170

AC XY:

109032

AN XY:

641186

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

8614

17228

25841

34455

43069

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6040

12080

18120

24160

30200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.203

AC:

30841

AN:

152118

Hom.:

3417

Cov.:

AF XY:

0.203

AC XY:

15082

AN XY:

74380

show subpopulations

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:

AN:

292

European-Non Finnish (NFE)

AF:

0.163

AC:

11056

AN:

67994

Other (OTH)

AF:

0.201

AC:

424

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1248

2495

3743

4990

6238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

318

636

954

1272

1590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.6

(source)

DANN

Benign

0.69

PhyloP100

-0.50

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over