rs7694646

Positions:

• chr4-99138581-T-A

Variant summary

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

The NM_000670.5(ADH4):​c.350+480A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,188 control chromosomes in the GnomAD database, including 4,039 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 0.21 (4039 hom., cov: 33)
• Consequence: ADH4 NM_000670.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288

Genes affected

ADH4 (HGNC:252): (alcohol dehydrogenase 4 (class II), pi polypeptide) This gene encodes class II alcohol dehydrogenase 4 pi subunit, which is a member of the alcohol dehydrogenase family. Members of this enzyme family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. Class II alcohol dehydrogenase is a homodimer composed of 2 pi subunits. It exhibits a high activity for oxidation of long-chain aliphatic alcohols and aromatic alcohols and is less sensitive to pyrazole. This gene is localized to chromosome 4 in the cluster of alcohol dehydrogenase genes. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH4	NM_000670.5	c.350+480A>T		intron_variant		ENST00000265512.12	NP_000661.2
LOC100507053	NR_037884.1	n.679+4776T>A		intron_variant, non_coding_transcript_variant
ADH4	NM_001306171.2	c.407+480A>T		intron_variant			NP_001293100.1
ADH4	NM_001306172.2	c.407+480A>T		intron_variant			NP_001293101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH4	ENST00000265512.12	c.350+480A>T		intron_variant		1	NM_000670.5	ENSP00000265512	P1
	ENST00000500358.6	n.679+4776T>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31976 AN: 152070 Hom.: 4042 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.239

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.210 AC: 31977 AN: 152188 Hom.: 4039 Cov.: 33 AF XY: 0.203 AC XY: 15073 AN XY: 74412

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.237

Alfa AF: 0.248 Hom.: 663

Bravo AF: 0.203

Asia WGS AF: 0.0680 AC: 239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.7
DANN	Benign	0.81

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: rs7694646; hg19: chr4-100059732;