rs1154470

chr4-99435180-G-Achr4-99435180-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000673.7(ADH7):c.18+36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,604,726 control chromosomes in the GnomAD database, including 87,217 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 0.28 (6558 hom., cov: 32)
  • Exomes 𝑓: 0.33 (80659 hom.)
• Consequence: ADH7 NM_000673.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH7	NM_000673.7	c.18+36C>T		intron_variant		ENST00000437033.7
ADH7	NM_001166504.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH7	ENST00000437033.7	c.18+36C>T		intron_variant		1	NM_000673.7	P1
ADH7	ENST00000209665.8	c.54+36C>T		intron_variant		1
ADH7	ENST00000482593.5	c.-267+36C>T		intron_variant		3
ADH7	ENST00000476959.5			upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.277 AC: 41995 AN: 151880 Hom.: 6550 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.277

GnomAD3 exomes AF: 0.325 AC: 78158 AN: 240378 Hom.: 13245 AF XY: 0.323 AC XY: 41945 AN XY: 129746

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.463

Gnomad ASJ exome AF: 0.237

Gnomad EAS exome AF: 0.258

Gnomad SAS exome AF: 0.297

Gnomad FIN exome AF: 0.352

Gnomad NFE exome AF: 0.333

Gnomad OTH exome AF: 0.339

GnomAD4 exome AF: 0.329 AC: 478122 AN: 1452730 Hom.: 80659 Cov.: 33 AF XY: 0.328 AC XY: 236572 AN XY: 722200

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.447

Gnomad4 ASJ exome AF: 0.239

Gnomad4 EAS exome AF: 0.246

Gnomad4 SAS exome AF: 0.299

Gnomad4 FIN exome AF: 0.353

Gnomad4 NFE exome AF: 0.338

Gnomad4 OTH exome AF: 0.328

GnomAD4 genome AF: 0.276 AC: 42019 AN: 151996 Hom.: 6558 Cov.: 32 AF XY: 0.281 AC XY: 20888 AN XY: 74270

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.277

Alfa AF: 0.302 Hom.: 1938

Bravo AF: 0.274

Asia WGS AF: 0.316 AC: 1101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.38
Dann	Benign	0.22

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: rs1154470; hg19: chr4-100356337; COSMIC: COSV52921971; COSMIC: COSV52921971;