rs1126672

Variant names:

• chr4-99126661-G-A
• rs1126672
• NM_000670.5:c.1051C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-99126661-G-A
• chr4-99126661-G-C
• chr4-99126661-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000670.5(ADH4):​c.1051C>T​(p.Leu351Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,610,126 control chromosomes in the GnomAD database, including 53,540 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 (4047 hom., cov: 32)
  • Exomes 𝑓: 0.25 (49493 hom.)
• Consequence: ADH4 NM_000670.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 40 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=0.021 with no splicing effect.
• 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 rank	MANE	Protein	UniProt
ADH4	NM_000670.5	c.1051C>T	p.Leu351Leu	synonymous_variant	Exon 8 of 9	ENST00000265512.12	NP_000661.2
ADH4	NM_001306171.2	c.1108C>T	p.Leu370Leu	synonymous_variant	Exon 9 of 10		NP_001293100.1
ADH4	NM_001306172.2	c.1108C>T	p.Leu370Leu	synonymous_variant	Exon 9 of 10		NP_001293101.1
LOC100507053	NR_037884.1	n.429-6894G>A		intron_variant	Intron 1 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH4	ENST00000265512.12	c.1051C>T	p.Leu351Leu	synonymous_variant	Exon 8 of 9	1	NM_000670.5	ENSP00000265512.7

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32040 AN: 152042 Hom.: 4050 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.240

GnomAD2 exomes AF: 0.208 AC: 52179 AN: 251012 AF XY: 0.214

Gnomad AFR exome AF: 0.105

Gnomad AMR exome AF: 0.137

Gnomad ASJ exome AF: 0.299

Gnomad EAS exome AF: 0.00114

Gnomad FIN exome AF: 0.235

Gnomad NFE exome AF: 0.284

Gnomad OTH exome AF: 0.243

GnomAD4 exome AF: 0.251 AC: 365928 AN: 1457966 Hom.: 49493 Cov.: 32 AF XY: 0.249 AC XY: 180803 AN XY: 725252

African (AFR) AF: 0.102 AC: 3417 AN: 33460

American (AMR) AF: 0.143 AC: 6388 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 7858 AN: 25966

East Asian (EAS) AF: 0.00154 AC: 61 AN: 39680

South Asian (SAS) AF: 0.129 AC: 11031 AN: 85792

European-Finnish (FIN) AF: 0.240 AC: 12781 AN: 53196

Middle Eastern (MID) AF: 0.243 AC: 1400 AN: 5750

European-Non Finnish (NFE) AF: 0.278 AC: 308534 AN: 1109294

Other (OTH) AF: 0.240 AC: 14458 AN: 60168

GnomAD4 genome AF: 0.211 AC: 32041 AN: 152160 Hom.: 4047 Cov.: 32 AF XY: 0.203 AC XY: 15096 AN XY: 74366

African (AFR) AF: 0.109 AC: 4534 AN: 41524

American (AMR) AF: 0.208 AC: 3182 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1037 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5186

South Asian (SAS) AF: 0.116 AC: 559 AN: 4824

European-Finnish (FIN) AF: 0.233 AC: 2468 AN: 10574

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

European-Non Finnish (NFE) AF: 0.285 AC: 19373 AN: 67974

Other (OTH) AF: 0.238 AC: 503 AN: 2114

Alfa AF: 0.255 Hom.: 18810

Bravo AF: 0.204

Asia WGS AF: 0.0680 AC: 238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.44
DANN	Benign	0.60
PhyloP100		0.021
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1126672; hg19: chr4-100047812; COSMIC: COSV55500862; COSMIC: COSV55500862;