4-99315218-G-A

Position:

• chr4-99315218-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000668.6(ADH1B):​c.567+680C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 152,518 control chromosomes in the GnomAD database, including 82 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 0.027 (82 hom., cov: 33)
  • Exomes 𝑓: 0.034 (0 hom.)
• Consequence: ADH1B NM_000668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.524

Genes affected

ADH1B (HGNC:250): (alcohol dehydrogenase 1B (class I), beta polypeptide) The protein encoded by this gene 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. This encoded protein, consisting of several homo- and heterodimers of alpha, beta, and gamma subunits, exhibits high activity for ethanol oxidation and plays a major role in ethanol catabolism. Three genes encoding alpha, beta and gamma subunits are tandemly organized in a genomic segment as a gene cluster. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0274 (4173/152130) while in subpopulation SAS AF= 0.0539 (260/4820). AF 95% confidence interval is 0.0486. There are 82 homozygotes in gnomad4. There are 2123 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 82 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH1B	NM_000668.6	c.567+680C>T		intron_variant		ENST00000305046.13
ADH1B	NM_001286650.2	c.447+680C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH1B	ENST00000305046.13	c.567+680C>T		intron_variant		1	NM_000668.6	P1

Frequencies

GnomAD3 genomes AF: 0.0274 AC: 4169 AN: 152012 Hom.: 82 Cov.: 33

Gnomad AFR AF: 0.00604

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0425

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0539

Gnomad FIN AF: 0.0555

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0325

Gnomad OTH AF: 0.0254

GnomAD4 exome AF: 0.0335 AC: 13 AN: 388 Hom.: 0 Cov.: 0 AF XY: 0.0303 AC XY: 6 AN XY: 198

Gnomad4 AMR exome AF: 0.0435

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.100

Gnomad4 NFE exome AF: 0.0313

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0274 AC: 4173 AN: 152130 Hom.: 82 Cov.: 33 AF XY: 0.0285 AC XY: 2123 AN XY: 74366

Gnomad4 AFR AF: 0.00602

Gnomad4 AMR AF: 0.0427

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0539

Gnomad4 FIN AF: 0.0555

Gnomad4 NFE AF: 0.0325

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0316 Hom.: 90

Bravo AF: 0.0267

Asia WGS AF: 0.0320 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.38
DANN	Benign	0.39

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: rs1789883; hg19: chr4-100236375;