4-99420486-G-A

Variant names:

• chr4-99420486-G-A
• rs1154460
• NM_000673.7:c.825+47C>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.825+47C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 1,568,066 control chromosomes in the GnomAD database, including 159,061 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 0.46 (16233 hom., cov: 32)
  • Exomes 𝑓: 0.45 (142828 hom.)
• Consequence: ADH7 NM_000673.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227
• Publications: 17 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH7	NM_000673.7	c.825+47C>T		intron_variant	Intron 6 of 8	ENST00000437033.7	NP_000664.3
ADH7	NM_001166504.2	c.885+47C>T		intron_variant	Intron 6 of 8		NP_001159976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH7	ENST00000437033.7	c.825+47C>T		intron_variant	Intron 6 of 8	1	NM_000673.7	ENSP00000414254.2
ADH7	ENST00000209665.8	c.861+47C>T		intron_variant	Intron 6 of 8	1		ENSP00000209665.4
ADH7	ENST00000476959.5	c.885+47C>T		intron_variant	Intron 6 of 8	2		ENSP00000420269.1
ADH7	ENST00000482593.5	c.654+47C>T		intron_variant	Intron 7 of 9	3		ENSP00000420613.1

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69694 AN: 151904 Hom.: 16201 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.454

GnomAD2 exomes AF: 0.454 AC: 109584 AN: 241404 AF XY: 0.447

Gnomad AFR exome AF: 0.473

Gnomad AMR exome AF: 0.574

Gnomad ASJ exome AF: 0.460

Gnomad EAS exome AF: 0.358

Gnomad FIN exome AF: 0.444

Gnomad NFE exome AF: 0.446

Gnomad OTH exome AF: 0.466

GnomAD4 exome AF: 0.447 AC: 632845 AN: 1416044 Hom.: 142828 Cov.: 26 AF XY: 0.445 AC XY: 313176 AN XY: 704200

African (AFR) AF: 0.475 AC: 15285 AN: 32204

American (AMR) AF: 0.560 AC: 24215 AN: 43230

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 11395 AN: 24960

East Asian (EAS) AF: 0.365 AC: 14333 AN: 39284

South Asian (SAS) AF: 0.401 AC: 33503 AN: 83466

European-Finnish (FIN) AF: 0.444 AC: 23431 AN: 52824

Middle Eastern (MID) AF: 0.436 AC: 2444 AN: 5608

European-Non Finnish (NFE) AF: 0.447 AC: 481135 AN: 1075914

Other (OTH) AF: 0.463 AC: 27104 AN: 58554

GnomAD4 genome AF: 0.459 AC: 69786 AN: 152022 Hom.: 16233 Cov.: 32 AF XY: 0.462 AC XY: 34314 AN XY: 74306

African (AFR) AF: 0.477 AC: 19779 AN: 41450

American (AMR) AF: 0.512 AC: 7814 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1553 AN: 3466

East Asian (EAS) AF: 0.381 AC: 1966 AN: 5166

South Asian (SAS) AF: 0.407 AC: 1960 AN: 4818

European-Finnish (FIN) AF: 0.445 AC: 4706 AN: 10570

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30386 AN: 67976

Other (OTH) AF: 0.456 AC: 963 AN: 2114

Alfa AF: 0.455 Hom.: 27423

Bravo AF: 0.469

Asia WGS AF: 0.446 AC: 1552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.57
DANN	Benign	0.44
PhyloP100		0.23
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: rs1154460; hg19: chr4-100341643; COSMIC: COSV52919647; COSMIC: COSV52919647;