rs1154469

Variant names:

• chr4-99435022-C-T
• rs1154469
• NM_000673.7:c.18+194G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-99435022-C-T
• chr4-99435022-C-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001166504.2(ADH7):​c.78+5G>A variant causes a splice region, 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. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.28 (6705 hom., cov: 32)
  • Exomes 𝑓: 0.33 (76524 hom.)
• Consequence: ADH7 NM_001166504.2 splice_region, intron
• Scores: Splicing: ADA: 0.9165
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166504.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH7	NM_000673.7	MANE Select	c.18+194G>A		intron	N/A	NP_000664.3	A0A0C4DG85
	ADH7	NM_001166504.2		c.78+5G>A		splice_region intron	N/A	NP_001159976.1	P40394-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH7	ENST00000437033.7	TSL:1 MANE Select	c.18+194G>A		intron	N/A	ENSP00000414254.2	A0A0C4DG85
	ADH7	ENST00000209665.8	TSL:1	c.54+194G>A		intron	N/A	ENSP00000209665.4	P40394-1
	ADH7	ENST00000476959.5	TSL:2	c.78+5G>A		splice_region intron	N/A	ENSP00000420269.1	P40394-2

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

GnomAD2 exomes AF: 0.328 AC: 48101 AN: 146714 AF XY: 0.322

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 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

African (AFR) AF: 0.136 AC: 4270 AN: 31510

American (AMR) AF: 0.437 AC: 15579 AN: 35686

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 6112 AN: 25132

East Asian (EAS) AF: 0.248 AC: 8839 AN: 35700

South Asian (SAS) AF: 0.298 AC: 23576 AN: 79132

European-Finnish (FIN) AF: 0.349 AC: 13316 AN: 38148

Middle Eastern (MID) AF: 0.263 AC: 1496 AN: 5688

European-Non Finnish (NFE) AF: 0.337 AC: 361573 AN: 1073936

Other (OTH) AF: 0.330 AC: 19051 AN: 57758

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

African (AFR) AF: 0.155 AC: 6444 AN: 41504

American (AMR) AF: 0.371 AC: 5651 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 854 AN: 3472

East Asian (EAS) AF: 0.268 AC: 1388 AN: 5174

South Asian (SAS) AF: 0.306 AC: 1473 AN: 4816

European-Finnish (FIN) AF: 0.355 AC: 3751 AN: 10552

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22455 AN: 67942

Other (OTH) AF: 0.279 AC: 590 AN: 2114

Alfa AF: 0.316 Hom.: 33211

Bravo AF: 0.282

Asia WGS AF: 0.318 AC: 1107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.9
DANN	Benign	0.52
PhyloP100		-0.24
PromoterAI		0.040	Neutral
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1154469; hg19: chr4-100356179;