rs1154459

Positions:

• chr4-99419946-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000437033.7(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 ENST00000437033.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.648

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=-0.91).
• 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/exons	MANE	Protein	UniProt
ADH7	NM_000673.7	c.825+587C>T		intron_variant		ENST00000437033.7	NP_000664.3
ADH7	NM_001166504.2	c.885+587C>T		intron_variant			NP_001159976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH7	ENST00000437033.7	c.825+587C>T		intron_variant		1	NM_000673.7	ENSP00000414254	P1
ADH7	ENST00000209665.8	c.861+587C>T		intron_variant		1		ENSP00000209665
ADH7	ENST00000476959.5	c.885+587C>T		intron_variant		2		ENSP00000420269
ADH7	ENST00000482593.5	c.654+587C>T		intron_variant		3		ENSP00000420613

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

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.277

Alfa AF: 0.323 Hom.: 9555

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

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: rs1154459; hg19: chr4-100341103;