4-99412399-G-A

Variant names:

• chr4-99412399-G-A
• rs284787
• NM_000673.7:c.*749C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000673.7(ADH7):​c.*749C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 151,908 control chromosomes in the GnomAD database, including 3,704 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 0.21 (3704 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ADH7 NM_000673.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• Publications: 15 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH7	NM_000673.7	c.*749C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000437033.7	NP_000664.3
ADH7	NM_001166504.2	c.*749C>T		3_prime_UTR_variant	Exon 9 of 9		NP_001159976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH7	ENST00000437033.7	c.*749C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_000673.7	ENSP00000414254.2
ADH7	ENST00000209665.8	c.*749C>T		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000209665.4

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31442 AN: 151792 Hom.: 3704 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.210

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.207 AC: 31451 AN: 151908 Hom.: 3704 Cov.: 32 AF XY: 0.208 AC XY: 15435 AN XY: 74222

African (AFR) AF: 0.134 AC: 5552 AN: 41440

American (AMR) AF: 0.200 AC: 3052 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 705 AN: 3468

East Asian (EAS) AF: 0.515 AC: 2661 AN: 5166

South Asian (SAS) AF: 0.354 AC: 1705 AN: 4820

European-Finnish (FIN) AF: 0.133 AC: 1409 AN: 10560

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.230 AC: 15590 AN: 67876

Other (OTH) AF: 0.210 AC: 443 AN: 2114

Alfa AF: 0.227 Hom.: 13322

Bravo AF: 0.209

Asia WGS AF: 0.295 AC: 1019 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.32
PhyloP100		-0.084
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: rs284787; hg19: chr4-100333556;