chr4-99313983-C-G

Variant names:

• chr4-99313983-C-G
• rs2018417
• NM_000668.6:c.666G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000668.6(ADH1B):​c.666G>C​(p.Ala222Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A222A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADH1B NM_000668.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=-2.7 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000668.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1B	NM_000668.6	MANE Select	c.666G>C	p.Ala222Ala	synonymous	Exon 6 of 9	NP_000659.2
	ADH1B	NM_001286650.2		c.546G>C	p.Ala182Ala	synonymous	Exon 7 of 10	NP_001273579.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1B	ENST00000305046.13	TSL:1 MANE Select	c.666G>C	p.Ala222Ala	synonymous	Exon 6 of 9	ENSP00000306606.8
	ADH1B	ENST00000625860.2	TSL:1	c.546G>C	p.Ala182Ala	synonymous	Exon 6 of 9	ENSP00000486614.1
	ADH1B	ENST00000506651.5	TSL:2	c.546G>C	p.Ala182Ala	synonymous	Exon 7 of 10	ENSP00000425998.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.66
DANN	Benign	0.56
PhyloP100		-2.7

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: rs2018417; hg19: chr4-100235140;