chr4-99412775-A-G

Position:

• chr4-99412775-A-G

Variant summary

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

The NM_000673.7(ADH7):​c.*373T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0615 in 173,784 control chromosomes in the GnomAD database, including 347 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 0.061 (304 hom., cov: 33)
  • Exomes 𝑓: 0.065 (43 hom.)
• Consequence: ADH7 NM_000673.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH7	NM_000673.7	c.*373T>C		3_prime_UTR_variant	9/9	ENST00000437033.7	NP_000664.3
ADH7	NM_001166504.2	c.*373T>C		3_prime_UTR_variant	9/9		NP_001159976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH7	ENST00000437033.7	c.*373T>C		3_prime_UTR_variant	9/9	1	NM_000673.7	ENSP00000414254	P1
ADH7	ENST00000209665.8	c.*373T>C		3_prime_UTR_variant	9/9	1		ENSP00000209665

Frequencies

GnomAD3 genomes AF: 0.0611 AC: 9298 AN: 152134 Hom.: 305 Cov.: 33

Gnomad AFR AF: 0.0519

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0612

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.0749

Gnomad SAS AF: 0.0995

Gnomad FIN AF: 0.0563

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0641

Gnomad OTH AF: 0.0593

GnomAD4 exome AF: 0.0645 AC: 1389 AN: 21530 Hom.: 43 Cov.: 0 AF XY: 0.0641 AC XY: 715 AN XY: 11158

Gnomad4 AFR exome AF: 0.0392

Gnomad4 AMR exome AF: 0.0753

Gnomad4 ASJ exome AF: 0.0508

Gnomad4 EAS exome AF: 0.0625

Gnomad4 SAS exome AF: 0.0836

Gnomad4 FIN exome AF: 0.0493

Gnomad4 NFE exome AF: 0.0666

Gnomad4 OTH exome AF: 0.0633

GnomAD4 genome AF: 0.0611 AC: 9301 AN: 152254 Hom.: 304 Cov.: 33 AF XY: 0.0609 AC XY: 4531 AN XY: 74438

Gnomad4 AFR AF: 0.0519

Gnomad4 AMR AF: 0.0612

Gnomad4 ASJ AF: 0.0620

Gnomad4 EAS AF: 0.0744

Gnomad4 SAS AF: 0.0988

Gnomad4 FIN AF: 0.0563

Gnomad4 NFE AF: 0.0642

Gnomad4 OTH AF: 0.0610

Alfa AF: 0.0621 Hom.: 374

Bravo AF: 0.0602

Asia WGS AF: 0.110 AC: 379 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.69

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: rs3805331; hg19: chr4-100333932;