4-99435022-C-T

Position:

• chr4-99435022-C-T

Variant summary

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

The NM_000673.7(ADH7):​c.18+194G>A 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 1,534,720 control chromosomes in the GnomAD database, including 83,229 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 (6705 hom., cov: 32)
  • Exomes 𝑓: 0.33 (76524 hom.)
• Consequence: ADH7 NM_000673.7 intron
• Scores: Splicing: ADA: 0.9165
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH7	NM_000673.7	c.18+194G>A		intron_variant		ENST00000437033.7	NP_000664.3
ADH7	NM_001166504.2	c.78+5G>A		splice_donor_5th_base_variant, intron_variant			NP_001159976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH7	ENST00000437033.7	c.18+194G>A		intron_variant		1	NM_000673.7	ENSP00000414254	P1
ADH7	ENST00000209665.8	c.54+194G>A		intron_variant		1		ENSP00000209665
ADH7	ENST00000476959.5	c.78+5G>A		splice_donor_5th_base_variant, intron_variant		2		ENSP00000420269
ADH7	ENST00000482593.5	c.-267+194G>A		intron_variant		3		ENSP00000420613

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43002 AN: 151910 Hom.: 6697 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.279

GnomAD3 exomes AF: 0.328 AC: 48101 AN: 146714 Hom.: 8333 AF XY: 0.322 AC XY: 25146 AN XY: 78078

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.455

Gnomad ASJ exome AF: 0.241

Gnomad EAS exome AF: 0.258

Gnomad SAS exome AF: 0.298

Gnomad FIN exome AF: 0.346

Gnomad NFE exome AF: 0.333

Gnomad OTH exome AF: 0.342

GnomAD4 exome AF: 0.328 AC: 453812 AN: 1382690 Hom.: 76524 Cov.: 30 AF XY: 0.327 AC XY: 223043 AN XY: 682660

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.437

Gnomad4 ASJ exome AF: 0.243

Gnomad4 EAS exome AF: 0.248

Gnomad4 SAS exome AF: 0.298

Gnomad4 FIN exome AF: 0.349

Gnomad4 NFE exome AF: 0.337

Gnomad4 OTH exome AF: 0.330

GnomAD4 genome AF: 0.283 AC: 43036 AN: 152030 Hom.: 6705 Cov.: 32 AF XY: 0.288 AC XY: 21367 AN XY: 74280

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.279

Alfa AF: 0.323 Hom.: 17020

Bravo AF: 0.282

Asia WGS AF: 0.318 AC: 1107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.9
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.92
dbscSNV1_RF	Benign	0.30
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: rs1154469; hg19: chr4-100356179;