rs3805331

Variant names:

• chr4-99412775-A-G
• rs3805331
• NM_000673.7:c.*373T>C

Variant summary

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

The NM_000673.7(ADH7):​c.*373T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0615 in 173,784 control chromosomes in the GnomAD database, including 347 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 0.061 (304 hom., cov: 33)
  • Exomes 𝑓: 0.065 (43 hom.)
• Consequence: ADH7 NM_000673.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440
• Publications: 8 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0914 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000673.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH7	NM_000673.7	MANE Select	c.*373T>C		3_prime_UTR	Exon 9 of 9	NP_000664.3
	ADH7	NM_001166504.2		c.*373T>C		3_prime_UTR	Exon 9 of 9	NP_001159976.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH7	ENST00000437033.7	TSL:1 MANE Select	c.*373T>C		3_prime_UTR	Exon 9 of 9	ENSP00000414254.2
	ADH7	ENST00000209665.8	TSL:1	c.*373T>C		3_prime_UTR	Exon 9 of 9	ENSP00000209665.4
	ADH7	ENST00000482593.5	TSL:3	c.*373T>C		downstream_gene	N/A	ENSP00000420613.1

Frequencies

GnomAD3 genomes AF: 0.0611 AC: 9298 AN: 152134 Hom.: 305 Cov.: 33

Gnomad AFR AF: 0.0519

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0612

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.0749

Gnomad SAS AF: 0.0995

Gnomad FIN AF: 0.0563

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0641

Gnomad OTH AF: 0.0593

GnomAD4 exome AF: 0.0645 AC: 1389 AN: 21530 Hom.: 43 Cov.: 0 AF XY: 0.0641 AC XY: 715 AN XY: 11158

African (AFR) AF: 0.0392 AC: 31 AN: 790

American (AMR) AF: 0.0753 AC: 61 AN: 810

Ashkenazi Jewish (ASJ) AF: 0.0508 AC: 40 AN: 788

East Asian (EAS) AF: 0.0625 AC: 89 AN: 1424

South Asian (SAS) AF: 0.0836 AC: 45 AN: 538

European-Finnish (FIN) AF: 0.0493 AC: 40 AN: 812

Middle Eastern (MID) AF: 0.0476 AC: 6 AN: 126

European-Non Finnish (NFE) AF: 0.0666 AC: 986 AN: 14804

Other (OTH) AF: 0.0633 AC: 91 AN: 1438

GnomAD4 genome AF: 0.0611 AC: 9301 AN: 152254 Hom.: 304 Cov.: 33 AF XY: 0.0609 AC XY: 4531 AN XY: 74438

African (AFR) AF: 0.0519 AC: 2157 AN: 41570

American (AMR) AF: 0.0612 AC: 936 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0620 AC: 215 AN: 3468

East Asian (EAS) AF: 0.0744 AC: 386 AN: 5186

South Asian (SAS) AF: 0.0988 AC: 476 AN: 4820

European-Finnish (FIN) AF: 0.0563 AC: 597 AN: 10604

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0642 AC: 4362 AN: 67990

Other (OTH) AF: 0.0610 AC: 129 AN: 2114

Alfa AF: 0.0619 Hom.: 432

Bravo AF: 0.0602

Asia WGS AF: 0.110 AC: 379 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.69
PhyloP100		0.44
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: rs3805331; hg19: chr4-100333932;