rs1154468

Variant names:

• chr4-99433100-T-A
• rs1154468
• NM_000673.7:c.18+2116A>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.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 NM_000673.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280
• Publications: 7 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 = 0.363 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000673.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH7	NM_000673.7	MANE Select	c.18+2116A>T		intron	N/A	NP_000664.3	A0A0C4DG85
	ADH7	NM_001166504.2		c.78+1927A>T		intron	N/A	NP_001159976.1	P40394-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH7	ENST00000437033.7	TSL:1 MANE Select	c.18+2116A>T		intron	N/A	ENSP00000414254.2	A0A0C4DG85
	ADH7	ENST00000209665.8	TSL:1	c.54+2116A>T		intron	N/A	ENSP00000209665.4	P40394-1
	ADH7	ENST00000476959.5	TSL:2	c.78+1927A>T		intron	N/A	ENSP00000420269.1	P40394-2

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

African (AFR) AF: 0.154 AC: 6385 AN: 41514

American (AMR) AF: 0.371 AC: 5654 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 854 AN: 3470

East Asian (EAS) AF: 0.269 AC: 1391 AN: 5176

South Asian (SAS) AF: 0.307 AC: 1482 AN: 4824

European-Finnish (FIN) AF: 0.355 AC: 3752 AN: 10576

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.330 AC: 22455 AN: 67952

Other (OTH) AF: 0.279 AC: 590 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.45
PhyloP100		-0.028
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: rs1154468; hg19: chr4-100354257;