4-99428309-T-C

Position:

• chr4-99428309-T-C

Variant summary

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

The NM_000673.7(ADH7):​c.260-135A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 1,219,384 control chromosomes in the GnomAD database, including 4,000 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 0.015 (419 hom., cov: 32)
  • Exomes 𝑓: 0.017 (3581 hom.)
• Consequence: ADH7 NM_000673.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.742

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH7	NM_000673.7	c.260-135A>G		intron_variant		ENST00000437033.7	NP_000664.3
ADH7	NM_001166504.2	c.320-135A>G		intron_variant			NP_001159976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH7	ENST00000437033.7	c.260-135A>G		intron_variant		1	NM_000673.7	ENSP00000414254.2

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2289 AN: 152192 Hom.: 420 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00173

Gnomad OTH AF: 0.00621

GnomAD4 exome AF: 0.0167 AC: 17770 AN: 1067074 Hom.: 3581 AF XY: 0.0162 AC XY: 8712 AN XY: 536384

Gnomad4 AFR exome AF: 0.000459

Gnomad4 AMR exome AF: 0.00123

Gnomad4 ASJ exome AF: 0.00540

Gnomad4 EAS exome AF: 0.442

Gnomad4 SAS exome AF: 0.00297

Gnomad4 FIN exome AF: 0.000112

Gnomad4 NFE exome AF: 0.00142

Gnomad4 OTH exome AF: 0.0125

GnomAD4 genome AF: 0.0150 AC: 2284 AN: 152310 Hom.: 419 Cov.: 32 AF XY: 0.0175 AC XY: 1304 AN XY: 74482

Gnomad4 AFR AF: 0.000433

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00173

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.00766 Hom.: 337

Bravo AF: 0.0184

Asia WGS AF: 0.0980 AC: 340 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.81
DANN	Benign	0.70

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: rs3737482; hg19: chr4-100349466; COSMIC: COSV52920080;