rs2213035

Variant names:

• chr4-99143082-G-A
• rs2213035
• NM_000670.5:c.19-302C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-99143082-G-A
• chr4-99143082-G-C

Variant summary

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

The NM_000670.5(ADH4):​c.19-302C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 693,344 control chromosomes in the GnomAD database, including 21,072 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 (4045 hom., cov: 31)
  • Exomes 𝑓: 0.23 (17027 hom.)
• Consequence: ADH4 NM_000670.5 intron
• Scores: Splicing: ADA: 0.00004877
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.607
• Publications: 3 publications found

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]

ENSG00000246090 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000670.5. 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
	ADH4	NM_000670.5	MANE Select	c.19-302C>T		intron	N/A	NP_000661.2	P08319-1
	ADH4	NM_001306171.2		c.75+84C>T		intron	N/A	NP_001293100.1	P08319-2
	ADH4	NM_001306172.2		c.75+84C>T		intron	N/A	NP_001293101.1	P08319-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH4	ENST00000265512.12	TSL:1 MANE Select	c.19-302C>T		intron	N/A	ENSP00000265512.7	P08319-1
	ENSG00000246090	ENST00000500358.6	TSL:1	n.679+9277G>A		intron	N/A
	ADH4	ENST00000505590.5	TSL:5	c.75+84C>T		intron	N/A	ENSP00000425416.1	P08319-2

Frequencies

GnomAD3 genomes AF: 0.211 AC: 31954 AN: 151604 Hom.: 4048 Cov.: 31

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.240

GnomAD2 exomes AF: 0.196 AC: 24929 AN: 127264 AF XY: 0.198

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.293

Gnomad EAS exome AF: 0.00135

Gnomad FIN exome AF: 0.225

Gnomad NFE exome AF: 0.283

Gnomad OTH exome AF: 0.234

GnomAD4 exome AF: 0.233 AC: 126109 AN: 541630 Hom.: 17027 Cov.: 0 AF XY: 0.231 AC XY: 67670 AN XY: 293462

African (AFR) AF: 0.109 AC: 1697 AN: 15552

American (AMR) AF: 0.150 AC: 5161 AN: 34320

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 5969 AN: 19706

East Asian (EAS) AF: 0.00157 AC: 50 AN: 31764

South Asian (SAS) AF: 0.129 AC: 7980 AN: 61704

European-Finnish (FIN) AF: 0.242 AC: 7909 AN: 32628

Middle Eastern (MID) AF: 0.249 AC: 998 AN: 4006

European-Non Finnish (NFE) AF: 0.286 AC: 89194 AN: 311880

Other (OTH) AF: 0.238 AC: 7151 AN: 30070

GnomAD4 genome AF: 0.211 AC: 31955 AN: 151714 Hom.: 4045 Cov.: 31 AF XY: 0.203 AC XY: 15055 AN XY: 74098

African (AFR) AF: 0.108 AC: 4478 AN: 41388

American (AMR) AF: 0.209 AC: 3174 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1035 AN: 3468

East Asian (EAS) AF: 0.00175 AC: 9 AN: 5148

South Asian (SAS) AF: 0.116 AC: 555 AN: 4802

European-Finnish (FIN) AF: 0.236 AC: 2464 AN: 10456

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19367 AN: 67934

Other (OTH) AF: 0.238 AC: 500 AN: 2104

Alfa AF: 0.255 Hom.: 1016

Bravo AF: 0.203

Asia WGS AF: 0.0680 AC: 237 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	7.6
DANN	Benign	0.29
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000049
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.040		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: rs2213035; hg19: chr4-100064233;