rs1154470

Variant names:

• chr4-99435180-G-A
• rs1154470
• NM_000673.7:c.18+36C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-99435180-G-A
• chr4-99435180-G-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.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
• Publications: 12 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=-0.92).
• 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 rank	MANE	Protein	UniProt
ADH7	NM_000673.7	c.18+36C>T		intron_variant	Intron 1 of 8	ENST00000437033.7	NP_000664.3
ADH7	NM_001166504.2	c.-76C>T		upstream_gene_variant			NP_001159976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH7	ENST00000437033.7	c.18+36C>T		intron_variant	Intron 1 of 8	1	NM_000673.7	ENSP00000414254.2
ADH7	ENST00000209665.8	c.54+36C>T		intron_variant	Intron 1 of 8	1		ENSP00000209665.4
ADH7	ENST00000482593.5	c.-267+36C>T		intron_variant	Intron 1 of 9	3		ENSP00000420613.1
ADH7	ENST00000476959.5	c.-76C>T		upstream_gene_variant		2		ENSP00000420269.1

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

GnomAD2 exomes AF: 0.325 AC: 78158 AN: 240378 AF XY: 0.323

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 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

African (AFR) AF: 0.114 AC: 3790 AN: 33298

American (AMR) AF: 0.447 AC: 19588 AN: 43834

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 6202 AN: 25934

East Asian (EAS) AF: 0.246 AC: 9716 AN: 39448

South Asian (SAS) AF: 0.299 AC: 25410 AN: 84984

European-Finnish (FIN) AF: 0.353 AC: 18729 AN: 53024

Middle Eastern (MID) AF: 0.263 AC: 1516 AN: 5756

European-Non Finnish (NFE) AF: 0.338 AC: 373492 AN: 1106488

Other (OTH) AF: 0.328 AC: 19679 AN: 59964

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

African (AFR) AF: 0.131 AC: 5451 AN: 41502

American (AMR) AF: 0.368 AC: 5615 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 844 AN: 3468

East Asian (EAS) AF: 0.269 AC: 1390 AN: 5166

South Asian (SAS) AF: 0.307 AC: 1482 AN: 4820

European-Finnish (FIN) AF: 0.356 AC: 3763 AN: 10556

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22458 AN: 67938

Other (OTH) AF: 0.277 AC: 584 AN: 2106

Alfa AF: 0.299 Hom.: 1946

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
PhyloP100		-1.1
PromoterAI		0.013	Neutral
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: rs1154470; hg19: chr4-100356337; COSMIC: COSV52921971; COSMIC: COSV52921971;