rs1154468

Positions:

• chr4-99433100-T-A

Variant summary

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

The ENST00000437033.7(ADH7):​c.18+2116A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,084 control chromosomes in the GnomAD database, including 6,698 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 0.28 (6698 hom., cov: 32)
• Consequence: ADH7 ENST00000437033.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280

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 = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH7	NM_000673.7	c.18+2116A>T		intron_variant		ENST00000437033.7	NP_000664.3
ADH7	NM_001166504.2	c.78+1927A>T		intron_variant			NP_001159976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH7	ENST00000437033.7	c.18+2116A>T		intron_variant		1	NM_000673.7	ENSP00000414254	P1
ADH7	ENST00000209665.8	c.54+2116A>T		intron_variant		1		ENSP00000209665
ADH7	ENST00000476959.5	c.78+1927A>T		intron_variant		2		ENSP00000420269
ADH7	ENST00000482593.5	c.-266-369A>T		intron_variant		3		ENSP00000420613

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42962 AN: 151966 Hom.: 6690 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.283 AC: 42993 AN: 152084 Hom.: 6698 Cov.: 32 AF XY: 0.287 AC XY: 21356 AN XY: 74324

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.279

Alfa AF: 0.299 Hom.: 904

Bravo AF: 0.282

Asia WGS AF: 0.318 AC: 1107 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	1.7
DANN	Benign	0.45

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: rs1154468; hg19: chr4-100354257;