4-99420486-G-A

Position:

• chr4-99420486-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ADH7	NM_000673.7	c.825+47C>T		intron_variant		ENST00000437033.7	NP_000664.3
ADH7	NM_001166504.2	c.885+47C>T		intron_variant			NP_001159976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH7	ENST00000437033.7	c.825+47C>T		intron_variant		1	NM_000673.7	ENSP00000414254	P1
ADH7	ENST00000209665.8	c.861+47C>T		intron_variant		1		ENSP00000209665
ADH7	ENST00000476959.5	c.885+47C>T		intron_variant		2		ENSP00000420269
ADH7	ENST00000482593.5	c.654+47C>T		intron_variant		3		ENSP00000420613

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

GnomAD3 exomes AF: 0.454 AC: 109584 AN: 241404 Hom.: 25203 AF XY: 0.447 AC XY: 58362 AN XY: 130434

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 SAS exome AF: 0.399

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

Gnomad4 AFR exome AF: 0.475

Gnomad4 AMR exome AF: 0.560

Gnomad4 ASJ exome AF: 0.457

Gnomad4 EAS exome AF: 0.365

Gnomad4 SAS exome AF: 0.401

Gnomad4 FIN exome AF: 0.444

Gnomad4 NFE exome AF: 0.447

Gnomad4 OTH exome AF: 0.463

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

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.407

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.456

Alfa AF: 0.453 Hom.: 21631

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1154460; hg19: chr4-100341643; COSMIC: COSV52919647; COSMIC: COSV52919647;