rs1154459

Variant names:

• chr4-99419946-G-A
• rs1154459
• NM_000673.7:c.825+587C>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.825+587C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,102 control chromosomes in the GnomAD database, including 6,319 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 0.27 (6319 hom., cov: 32)
• Consequence: ADH7 NM_000673.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.648
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH7	NM_000673.7	c.825+587C>T		intron_variant	Intron 6 of 8	ENST00000437033.7	NP_000664.3
ADH7	NM_001166504.2	c.885+587C>T		intron_variant	Intron 6 of 8		NP_001159976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH7	ENST00000437033.7	c.825+587C>T		intron_variant	Intron 6 of 8	1	NM_000673.7	ENSP00000414254.2
ADH7	ENST00000209665.8	c.861+587C>T		intron_variant	Intron 6 of 8	1		ENSP00000209665.4
ADH7	ENST00000476959.5	c.885+587C>T		intron_variant	Intron 6 of 8	2		ENSP00000420269.1
ADH7	ENST00000482593.5	c.654+587C>T		intron_variant	Intron 7 of 9	3		ENSP00000420613.1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41263 AN: 151984 Hom.: 6311 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.271 AC: 41287 AN: 152102 Hom.: 6319 Cov.: 32 AF XY: 0.275 AC XY: 20416 AN XY: 74340

African (AFR) AF: 0.131 AC: 5456 AN: 41532

American (AMR) AF: 0.369 AC: 5624 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 832 AN: 3472

East Asian (EAS) AF: 0.267 AC: 1378 AN: 5168

South Asian (SAS) AF: 0.304 AC: 1463 AN: 4816

European-Finnish (FIN) AF: 0.302 AC: 3191 AN: 10568

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22329 AN: 67980

Other (OTH) AF: 0.277 AC: 583 AN: 2106

Alfa AF: 0.317 Hom.: 11515

Bravo AF: 0.273

Asia WGS AF: 0.313 AC: 1090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.53
PhyloP100		0.65
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: rs1154459; hg19: chr4-100341103;