chr4-99124423-T-C

Variant names:

• chr4-99124423-T-C
• rs1042364
• ENST00000265512:c.*19A>G

Variant summary

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

The NM_000670.5(ADH4):​c.*19A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 1,459,260 control chromosomes in the GnomAD database, including 408,810 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 0.79 (48068 hom., cov: 32)
  • Exomes 𝑓: 0.74 (360742 hom.)
• Consequence: ADH4 NM_000670.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.500

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 (MetaRNN=9.252315E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH4	NM_000670.5	c.*19A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000265512.12	NP_000661.2
ADH4	NM_001306171.2	c.*19A>G		3_prime_UTR_variant	Exon 10 of 10		NP_001293100.1
ADH4	NM_001306172.2	c.*19A>G		3_prime_UTR_variant	Exon 10 of 10		NP_001293101.1
LOC100507053	NR_037884.1	n.429-9132T>C		intron_variant	Intron 1 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH4	ENST00000265512	c.*19A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_000670.5	ENSP00000265512.7

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119970 AN: 152018 Hom.: 48014 Cov.: 32

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.883

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.760

GnomAD2 exomes AF: 0.785 AC: 182653 AN: 232700 AF XY: 0.779

Gnomad AFR exome AF: 0.892

Gnomad AMR exome AF: 0.858

Gnomad ASJ exome AF: 0.698

Gnomad EAS exome AF: 0.999

Gnomad FIN exome AF: 0.764

Gnomad NFE exome AF: 0.709

Gnomad OTH exome AF: 0.749

GnomAD4 exome AF: 0.736 AC: 962632 AN: 1307124 Hom.: 360742 Cov.: 23 AF XY: 0.739 AC XY: 484269 AN XY: 655170

Gnomad4 AFR exome AF: 0.893 AC: 26478 AN: 29662

Gnomad4 AMR exome AF: 0.852 AC: 35394 AN: 41518

Gnomad4 ASJ exome AF: 0.690 AC: 17221 AN: 24956

Gnomad4 EAS exome AF: 0.998 AC: 37632 AN: 37690

Gnomad4 SAS exome AF: 0.864 AC: 66525 AN: 77030

Gnomad4 FIN exome AF: 0.758 AC: 40040 AN: 52798

Gnomad4 NFE exome AF: 0.706 AC: 694280 AN: 983266

Gnomad4 Remaining exome AF: 0.748 AC: 41100 AN: 54926

GnomAD4 genome AF: 0.789 AC: 120085 AN: 152136 Hom.: 48068 Cov.: 32 AF XY: 0.797 AC XY: 59253 AN XY: 74358

Gnomad4 AFR AF: 0.891 AC: 0.890578 AN: 0.890578

Gnomad4 AMR AF: 0.792 AC: 0.792092 AN: 0.792092

Gnomad4 ASJ AF: 0.701 AC: 0.701037 AN: 0.701037

Gnomad4 EAS AF: 0.998 AC: 0.998261 AN: 0.998261

Gnomad4 SAS AF: 0.883 AC: 0.883451 AN: 0.883451

Gnomad4 FIN AF: 0.767 AC: 0.766635 AN: 0.766635

Gnomad4 NFE AF: 0.715 AC: 0.714983 AN: 0.714983

Gnomad4 OTH AF: 0.763 AC: 0.762559 AN: 0.762559

Alfa AF: 0.742 Hom.: 95795

Bravo AF: 0.796

TwinsUK AF: 0.716 AC: 2654

ALSPAC AF: 0.723 AC: 2786

ESP6500AA AF: 0.890 AC: 3916

ESP6500EA AF: 0.711 AC: 6113

ExAC AF: 0.784 AC: 95124

Asia WGS AF: 0.932 AC: 3237 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.3
DANN	Benign	0.69
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	9.3e-7	T
Vest4		0.11
GERP RS		2.3
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

Publications

LitVar

Other links and lift over

dbSNP: rs1042364; hg19: chr4-100045574;