rs2584464

Variant names:

• chr4-99417892-G-A
• rs2584464
• NM_000673.7:c.961+1094C>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.961+1094C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,980 control chromosomes in the GnomAD database, including 15,701 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 0.45 (15701 hom., cov: 32)
• Consequence: ADH7 NM_000673.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.695
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) 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.961+1094C>T		intron_variant	Intron 7 of 8	ENST00000437033.7	NP_000664.3
ADH7	NM_001166504.2	c.1021+1094C>T		intron_variant	Intron 7 of 8		NP_001159976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH7	ENST00000437033.7	c.961+1094C>T		intron_variant	Intron 7 of 8	1	NM_000673.7	ENSP00000414254.2
ADH7	ENST00000209665.8	c.997+1094C>T		intron_variant	Intron 7 of 8	1		ENSP00000209665.4
ADH7	ENST00000476959.5	c.1021+1094C>T		intron_variant	Intron 7 of 8	2		ENSP00000420269.1
ADH7	ENST00000482593.5	c.790+1094C>T		intron_variant	Intron 8 of 9	3		ENSP00000420613.1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67730 AN: 151860 Hom.: 15669 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.441

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.446 AC: 67817 AN: 151980 Hom.: 15701 Cov.: 32 AF XY: 0.451 AC XY: 33501 AN XY: 74296

African (AFR) AF: 0.334 AC: 13826 AN: 41412

American (AMR) AF: 0.508 AC: 7761 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1253 AN: 3470

East Asian (EAS) AF: 0.380 AC: 1968 AN: 5182

South Asian (SAS) AF: 0.486 AC: 2343 AN: 4818

European-Finnish (FIN) AF: 0.524 AC: 5521 AN: 10540

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.494 AC: 33556 AN: 67976

Other (OTH) AF: 0.445 AC: 941 AN: 2114

Alfa AF: 0.476 Hom.: 5979

Bravo AF: 0.440

Asia WGS AF: 0.482 AC: 1675 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.34
DANN	Benign	0.16
PhyloP100		-0.69
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: rs2584464; hg19: chr4-100339049;