chr4-99413292-T-A

Position:

• chr4-99413292-T-A

Variant summary

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

The NM_000673.7(ADH7):​c.1101-120A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 1,096,422 control chromosomes in the GnomAD database, including 16,712 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 0.15 (1925 hom., cov: 32)
  • Exomes 𝑓: 0.17 (14787 hom.)
• Consequence: ADH7 NM_000673.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.744

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH7	NM_000673.7	c.1101-120A>T		intron_variant		ENST00000437033.7
ADH7	NM_001166504.2	c.1161-120A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH7	ENST00000437033.7	c.1101-120A>T		intron_variant		1	NM_000673.7	P1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23163 AN: 152116 Hom.: 1918 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0177

Gnomad SAS AF: 0.0710

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.130

GnomAD4 exome AF: 0.168 AC: 158663 AN: 944188 Hom.: 14787 AF XY: 0.165 AC XY: 80235 AN XY: 485824

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.0930

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.0224

Gnomad4 SAS exome AF: 0.0665

Gnomad4 FIN exome AF: 0.185

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.149

GnomAD4 genome AF: 0.152 AC: 23193 AN: 152234 Hom.: 1925 Cov.: 32 AF XY: 0.148 AC XY: 11033 AN XY: 74434

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.0176

Gnomad4 SAS AF: 0.0725

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.128

Alfa AF: 0.179 Hom.: 338

Bravo AF: 0.147

Asia WGS AF: 0.0510 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.1
DANN	Benign	0.79

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: rs17588403; hg19: chr4-100334449;