chr4-99130668-C-T

Position:

• chr4-99130668-C-T

Variant summary

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

The NM_000670.5(ADH4):​c.843+836G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 152,014 control chromosomes in the GnomAD database, including 43,127 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 0.75 (43127 hom., cov: 31)
• Consequence: ADH4 NM_000670.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH4	NM_000670.5	c.843+836G>A		intron_variant		ENST00000265512.12	NP_000661.2
LOC100507053	NR_037884.1	n.429-2887C>T		intron_variant, non_coding_transcript_variant
ADH4	NM_001306171.2	c.900+836G>A		intron_variant			NP_001293100.1
ADH4	NM_001306172.2	c.900+836G>A		intron_variant			NP_001293101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH4	ENST00000265512.12	c.843+836G>A		intron_variant		1	NM_000670.5	ENSP00000265512	P1
	ENST00000500358.6	n.429-2887C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113669 AN: 151896 Hom.: 43080 Cov.: 31

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.748 AC: 113777 AN: 152014 Hom.: 43127 Cov.: 31 AF XY: 0.756 AC XY: 56217 AN XY: 74312

Gnomad4 AFR AF: 0.825

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.674

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.863

Gnomad4 FIN AF: 0.712

Gnomad4 NFE AF: 0.686

Gnomad4 OTH AF: 0.731

Alfa AF: 0.699 Hom.: 25760

Bravo AF: 0.753

Asia WGS AF: 0.909 AC: 3154 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.33

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: rs4699710; hg19: chr4-100051819;