rs1827567

Positions:

• chr4-99414945-G-A
• chr4-99414945-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.1100+533C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,158 control chromosomes in the GnomAD database, including 3,835 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 0.21 (3835 hom., cov: 32)
• Consequence: ADH7 NM_000673.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166

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 (EAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH7	NM_000673.7	c.1100+533C>T		intron_variant		ENST00000437033.7	NP_000664.3
ADH7	NM_001166504.2	c.1160+533C>T		intron_variant			NP_001159976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH7	ENST00000437033.7	c.1100+533C>T		intron_variant		1	NM_000673.7	ENSP00000414254	P1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32311 AN: 152040 Hom.: 3833 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.215

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.212 AC: 32324 AN: 152158 Hom.: 3835 Cov.: 32 AF XY: 0.213 AC XY: 15818 AN XY: 74374

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.215

Alfa AF: 0.235 Hom.: 5450

Bravo AF: 0.216

Asia WGS AF: 0.296 AC: 1026 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	1.4
DANN	Benign	0.23

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: rs1827567; hg19: chr4-100336102;