4-99414826-T-C

Variant names:

• chr4-99414826-T-C
• rs2851011
• NM_000673.7:c.1100+652A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000673.7(ADH7):​c.1100+652A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 152,072 control chromosomes in the GnomAD database, including 45,198 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 0.77 (45198 hom., cov: 31)
• Consequence: ADH7 NM_000673.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.803 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.1100+652A>G		intron	N/A	NP_000664.3	A0A0C4DG85
	ADH7	NM_001166504.2		c.1160+652A>G		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.1100+652A>G		intron	N/A	ENSP00000414254.2	A0A0C4DG85
	ADH7	ENST00000209665.8	TSL:1	c.1136+652A>G		intron	N/A	ENSP00000209665.4	P40394-1
	ADH7	ENST00000476959.5	TSL:2	c.1160+652A>G		intron	N/A	ENSP00000420269.1	P40394-2

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116605 AN: 151954 Hom.: 45174 Cov.: 31

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.725

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

GnomAD4 genome AF: 0.767 AC: 116680 AN: 152072 Hom.: 45198 Cov.: 31 AF XY: 0.762 AC XY: 56620 AN XY: 74344

African (AFR) AF: 0.811 AC: 33631 AN: 41488

American (AMR) AF: 0.606 AC: 9254 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2350 AN: 3470

East Asian (EAS) AF: 0.648 AC: 3349 AN: 5172

South Asian (SAS) AF: 0.715 AC: 3442 AN: 4814

European-Finnish (FIN) AF: 0.770 AC: 8145 AN: 10576

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.795 AC: 54076 AN: 67980

Other (OTH) AF: 0.721 AC: 1518 AN: 2104

Alfa AF: 0.788 Hom.: 9573

Bravo AF: 0.754

Asia WGS AF: 0.605 AC: 2105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.51
PhyloP100		-0.96
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: rs2851011; hg19: chr4-100335983;