chr4-99428309-T-C

Variant summary

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

The NM_000673.7(ADH7):​c.260-135A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 1,219,384 control chromosomes in the GnomAD database, including 4,000 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 0.015 ( 419 hom., cov: 32)
Exomes 𝑓: 0.017 ( 3581 hom. )

Consequence

ADH7
NM_000673.7 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.742

Publications

4 publications found
Variant links:
Genes affected
ADH7 (HGNC:256): (alcohol dehydrogenase 7 (class IV), mu or sigma polypeptide) This gene encodes class IV alcohol dehydrogenase 7 mu or sigma subunit, which is a member of the alcohol dehydrogenase family. Members of this family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. The enzyme encoded by this gene is inefficient in ethanol oxidation, but is the most active as a retinol dehydrogenase; thus it may participate in the synthesis of retinoic acid, a hormone important for cellular differentiation. The expression of this gene is much more abundant in stomach than liver, thus differing from the other known gene family members. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

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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=-0.87).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADH7NM_000673.7 linkc.260-135A>G intron_variant Intron 3 of 8 ENST00000437033.7 NP_000664.3 P40394
ADH7NM_001166504.2 linkc.320-135A>G intron_variant Intron 3 of 8 NP_001159976.1 P40394-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADH7ENST00000437033.7 linkc.260-135A>G intron_variant Intron 3 of 8 1 NM_000673.7 ENSP00000414254.2 A0A0C4DG85

Frequencies

GnomAD3 genomes
AF:
0.0150
AC:
2289
AN:
152192
Hom.:
420
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000434
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00216
Gnomad ASJ
AF:
0.00749
Gnomad EAS
AF:
0.396
Gnomad SAS
AF:
0.00517
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.00173
Gnomad OTH
AF:
0.00621
GnomAD4 exome
AF:
0.0167
AC:
17770
AN:
1067074
Hom.:
3581
AF XY:
0.0162
AC XY:
8712
AN XY:
536384
show subpopulations
African (AFR)
AF:
0.000459
AC:
11
AN:
23944
American (AMR)
AF:
0.00123
AC:
35
AN:
28532
Ashkenazi Jewish (ASJ)
AF:
0.00540
AC:
106
AN:
19614
East Asian (EAS)
AF:
0.442
AC:
15700
AN:
35538
South Asian (SAS)
AF:
0.00297
AC:
189
AN:
63588
European-Finnish (FIN)
AF:
0.000112
AC:
5
AN:
44598
Middle Eastern (MID)
AF:
0.00176
AC:
8
AN:
4546
European-Non Finnish (NFE)
AF:
0.00142
AC:
1135
AN:
800162
Other (OTH)
AF:
0.0125
AC:
581
AN:
46552
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
581
1162
1744
2325
2906
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
184
368
552
736
920
<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:
0.0150
AC:
2284
AN:
152310
Hom.:
419
Cov.:
32
AF XY:
0.0175
AC XY:
1304
AN XY:
74482
show subpopulations
African (AFR)
AF:
0.000433
AC:
18
AN:
41596
American (AMR)
AF:
0.00216
AC:
33
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
0.00749
AC:
26
AN:
3470
East Asian (EAS)
AF:
0.396
AC:
2048
AN:
5170
South Asian (SAS)
AF:
0.00518
AC:
25
AN:
4828
European-Finnish (FIN)
AF:
0.0000941
AC:
1
AN:
10630
Middle Eastern (MID)
AF:
0.00680
AC:
2
AN:
294
European-Non Finnish (NFE)
AF:
0.00173
AC:
118
AN:
68014
Other (OTH)
AF:
0.00614
AC:
13
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
68
135
203
270
338
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
40
80
120
160
200
<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:
0.00676
Hom.:
424
Bravo
AF:
0.0184
Asia WGS
AF:
0.0980
AC:
340
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
0.81
DANN
Benign
0.70
PhyloP100
-0.74
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

Publications

Other links and lift over

dbSNP: rs3737482; hg19: chr4-100349466; COSMIC: COSV52920080; API