rs284787

Positions:

• chr4-99412399-G-A
• chr4-99412399-G-C
• chr4-99412399-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ADH7	NM_000673.7	c.*749C>T		3_prime_UTR_variant	9/9	ENST00000437033.7	NP_000664.3
ADH7	NM_001166504.2	c.*749C>T		3_prime_UTR_variant	9/9		NP_001159976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH7	ENST00000437033.7	c.*749C>T		3_prime_UTR_variant	9/9	1	NM_000673.7	ENSP00000414254	P1
ADH7	ENST00000209665.8	c.*749C>T		3_prime_UTR_variant	9/9	1		ENSP00000209665

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

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

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.210

Alfa AF: 0.229 Hom.: 4869

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

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

LitVar

Other links and lift over

dbSNP: rs284787; hg19: chr4-100333556;