chr4-99419073-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000673.7(ADH7):​c.874G>A​(p.Val292Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ADH7
NM_000673.7 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.416
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13552377).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADH7NM_000673.7 linkuse as main transcriptc.874G>A p.Val292Ile missense_variant 7/9 ENST00000437033.7
ADH7NM_001166504.2 linkuse as main transcriptc.934G>A p.Val312Ile missense_variant 7/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADH7ENST00000437033.7 linkuse as main transcriptc.874G>A p.Val292Ile missense_variant 7/91 NM_000673.7 P1
ADH7ENST00000209665.8 linkuse as main transcriptc.910G>A p.Val304Ile missense_variant 7/91 P40394-1
ADH7ENST00000476959.5 linkuse as main transcriptc.934G>A p.Val312Ile missense_variant 7/92 P40394-2
ADH7ENST00000482593.5 linkuse as main transcriptc.703G>A p.Val235Ile missense_variant 8/103

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152222
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000359
AC:
9
AN:
250964
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135630
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000261
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1461532
Hom.:
0
Cov.:
30
AF XY:
0.0000124
AC XY:
9
AN XY:
727074
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000197
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.00000656
AC:
1
AN:
152340
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000494
AC:
6

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 07, 2022The c.910G>A (p.V304I) alteration is located in exon 7 (coding exon 7) of the ADH7 gene. This alteration results from a G to A substitution at nucleotide position 910, causing the valine (V) at amino acid position 304 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
9.7
DANN
Benign
0.90
DEOGEN2
Benign
0.038
T;T;.;.
Eigen
Benign
-0.84
Eigen_PC
Benign
-0.88
FATHMM_MKL
Benign
0.054
N
LIST_S2
Benign
0.83
T;T;T;T
M_CAP
Benign
0.0032
T
MetaRNN
Benign
0.14
T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.62
N;.;.;.
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-0.43
N;N;N;N
REVEL
Benign
0.090
Sift
Benign
0.56
T;T;T;T
Sift4G
Benign
0.89
T;T;T;T
Polyphen
0.39
B;.;.;.
Vest4
0.23
MutPred
0.59
Loss of glycosylation at S309 (P = 0.1502);.;.;.;
MVP
0.29
MPC
0.020
ClinPred
0.061
T
GERP RS
1.9
Varity_R
0.083
gMVP
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs536459748; hg19: chr4-100340230; API