rs1154454

Variant names:

• chr4-99417185-A-G
• rs1154454
• NM_000673.7:c.962-1569T>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.962-1569T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 151,876 control chromosomes in the GnomAD database, including 4,793 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 0.22 (4793 hom., cov: 31)
• Consequence: ADH7 NM_000673.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352
• Publications: 9 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 (AFR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH7	NM_000673.7	c.962-1569T>C		intron_variant	Intron 7 of 8	ENST00000437033.7	NP_000664.3
ADH7	NM_001166504.2	c.1022-1569T>C		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.962-1569T>C		intron_variant	Intron 7 of 8	1	NM_000673.7	ENSP00000414254.2
ADH7	ENST00000209665.8	c.998-1569T>C		intron_variant	Intron 7 of 8	1		ENSP00000209665.4
ADH7	ENST00000476959.5	c.1022-1569T>C		intron_variant	Intron 7 of 8	2		ENSP00000420269.1
ADH7	ENST00000482593.5	c.791-1569T>C		intron_variant	Intron 8 of 9	3		ENSP00000420613.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32828 AN: 151758 Hom.: 4785 Cov.: 31

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0971

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.216 AC: 32872 AN: 151876 Hom.: 4793 Cov.: 31 AF XY: 0.210 AC XY: 15608 AN XY: 74266

African (AFR) AF: 0.410 AC: 16947 AN: 41346

American (AMR) AF: 0.133 AC: 2031 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0878 AC: 305 AN: 3472

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5166

South Asian (SAS) AF: 0.0962 AC: 462 AN: 4804

European-Finnish (FIN) AF: 0.107 AC: 1133 AN: 10570

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11294 AN: 67942

Other (OTH) AF: 0.194 AC: 409 AN: 2110

Alfa AF: 0.175 Hom.: 5898

Bravo AF: 0.226

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.81
DANN	Benign	0.53
PhyloP100		-0.35
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: rs1154454; hg19: chr4-100338342;