chr4-99414717-C-A

Variant names:

• chr4-99414717-C-A
• rs284784
• NM_000673.7:c.1100+761G>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.1100+761G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,062 control chromosomes in the GnomAD database, including 3,618 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 0.20 (3618 hom., cov: 32)
• Consequence: ADH7 NM_000673.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.496 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH7	NM_000673.7	MANE Select	c.1100+761G>T		intron	N/A	NP_000664.3
	ADH7	NM_001166504.2		c.1160+761G>T		intron	N/A	NP_001159976.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH7	ENST00000437033.7	TSL:1 MANE Select	c.1100+761G>T		intron	N/A	ENSP00000414254.2
	ADH7	ENST00000209665.8	TSL:1	c.1136+761G>T		intron	N/A	ENSP00000209665.4
	ADH7	ENST00000476959.5	TSL:2	c.1160+761G>T		intron	N/A	ENSP00000420269.1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30866 AN: 151944 Hom.: 3616 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.203 AC: 30878 AN: 152062 Hom.: 3618 Cov.: 32 AF XY: 0.204 AC XY: 15163 AN XY: 74334

African (AFR) AF: 0.121 AC: 5019 AN: 41480

American (AMR) AF: 0.199 AC: 3035 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 705 AN: 3466

East Asian (EAS) AF: 0.512 AC: 2650 AN: 5174

South Asian (SAS) AF: 0.354 AC: 1706 AN: 4818

European-Finnish (FIN) AF: 0.133 AC: 1405 AN: 10560

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15582 AN: 67982

Other (OTH) AF: 0.208 AC: 440 AN: 2112

Alfa AF: 0.229 Hom.: 2190

Bravo AF: 0.205

Asia WGS AF: 0.294 AC: 1022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.64
PhyloP100		-0.020
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: rs284784; hg19: chr4-100335874;