rs4148884

Positions:

• chr4-99145136-C-T

Variant summary

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

The NR_037884.1(LOC100507053):​n.680-9409C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,084 control chromosomes in the GnomAD database, including 2,724 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 0.16 (2724 hom., cov: 32)
• Consequence: LOC100507053 NR_037884.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC100507053	NR_037884.1	n.680-9409C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000500358.6	n.680-9409C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24224 AN: 151966 Hom.: 2719 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.0601

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0786

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.160 AC: 24259 AN: 152084 Hom.: 2724 Cov.: 32 AF XY: 0.162 AC XY: 12013 AN XY: 74354

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.0878

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.0608

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.0787

Gnomad4 OTH AF: 0.139

Alfa AF: 0.101 Hom.: 1439

Bravo AF: 0.180

Asia WGS AF: 0.142 AC: 495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.95
DANN	Benign	0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4148884; hg19: chr4-100066287;