4-99427779-A-T

Variant names:

• chr4-99427779-A-T
• rs370255803
• NM_000673.7:c.558T>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000673.7(ADH7):​c.558T>A​(p.Thr186Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,382,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T186T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: ADH7 NM_000673.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-0.309 with no splicing effect.

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.558T>A	p.Thr186Thr	synonymous	Exon 5 of 9	NP_000664.3	A0A0C4DG85
	ADH7	NM_001166504.2		c.618T>A	p.Thr206Thr	synonymous	Exon 5 of 9	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.558T>A	p.Thr186Thr	synonymous	Exon 5 of 9	ENSP00000414254.2	A0A0C4DG85
	ADH7	ENST00000209665.8	TSL:1	c.594T>A	p.Thr198Thr	synonymous	Exon 5 of 9	ENSP00000209665.4	P40394-1
	ADH7	ENST00000476959.5	TSL:2	c.618T>A	p.Thr206Thr	synonymous	Exon 5 of 9	ENSP00000420269.1	P40394-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000434 AC: 6 AN: 1382324 Hom.: 0 Cov.: 32 AF XY: 0.00000589 AC XY: 4 AN XY: 679050

African (AFR) AF: 0.00 AC: 0 AN: 31040

American (AMR) AF: 0.00 AC: 0 AN: 33006

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21828

East Asian (EAS) AF: 0.00 AC: 0 AN: 38600

South Asian (SAS) AF: 0.0000279 AC: 2 AN: 71646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51020

Middle Eastern (MID) AF: 0.000184 AC: 1 AN: 5422

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1072884

Other (OTH) AF: 0.0000176 AC: 1 AN: 56878

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.51
PhyloP100		-0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs370255803; hg19: chr4-100348936;