NM_000671.4:c.825+264G>C

Variant names:

• chr4-99076028-C-G
• rs4699699
• NM_000671.4:c.825+264G>C

Variant summary

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

The NM_000671.4(ADH5):​c.825+264G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0815 in 406,130 control chromosomes in the GnomAD database, including 1,594 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 0.084 (577 hom., cov: 32)
  • Exomes 𝑓: 0.080 (1017 hom.)
• Consequence: ADH5 NM_000671.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.833
• Publications: 4 publications found

Genes affected

ADH5 (HGNC:253): (alcohol dehydrogenase 5 (class III), chi polypeptide) This gene encodes a member of the alcohol dehydrogenase family. Members of this family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. The encoded protein forms a homodimer. It has virtually no activity for ethanol oxidation, but exhibits high activity for oxidation of long-chain primary alcohols and for oxidation of S-hydroxymethyl-glutathione, a spontaneous adduct between formaldehyde and glutathione. This enzyme is an important component of cellular metabolism for the elimination of formaldehyde, a potent irritant and sensitizing agent that causes lacrymation, rhinitis, pharyngitis, and contact dermatitis. The human genome contains several non-transcribed pseudogenes related to this gene. [provided by RefSeq, Oct 2008]

ADH5 Gene-Disease associations (from GenCC):

• AMED syndrome, digenic

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0983 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000671.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH5	NM_000671.4	MANE Select	c.825+264G>C		intron	N/A	NP_000662.3	P11766

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH5	ENST00000296412.14	TSL:1 MANE Select	c.825+264G>C		intron	N/A	ENSP00000296412.8	P11766
	ADH5	ENST00000885760.1		c.825+264G>C		intron	N/A	ENSP00000555819.1
	ADH5	ENST00000929295.1		c.829+260G>C		intron	N/A	ENSP00000599354.1

Frequencies

GnomAD3 genomes AF: 0.0841 AC: 12795 AN: 152128 Hom.: 577 Cov.: 32

Gnomad AFR AF: 0.0829

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0857

Gnomad ASJ AF: 0.0861

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0348

Gnomad FIN AF: 0.0447

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.0992

GnomAD4 exome AF: 0.0800 AC: 20304 AN: 253884 Hom.: 1017 Cov.: 3 AF XY: 0.0762 AC XY: 10252 AN XY: 134498

African (AFR) AF: 0.0800 AC: 618 AN: 7724

American (AMR) AF: 0.0716 AC: 726 AN: 10134

Ashkenazi Jewish (ASJ) AF: 0.0896 AC: 688 AN: 7680

East Asian (EAS) AF: 0.000207 AC: 3 AN: 14458

South Asian (SAS) AF: 0.0335 AC: 1071 AN: 31950

European-Finnish (FIN) AF: 0.0507 AC: 623 AN: 12288

Middle Eastern (MID) AF: 0.0833 AC: 89 AN: 1068

European-Non Finnish (NFE) AF: 0.0988 AC: 15224 AN: 154146

Other (OTH) AF: 0.0874 AC: 1262 AN: 14436

GnomAD4 genome AF: 0.0841 AC: 12803 AN: 152246 Hom.: 577 Cov.: 32 AF XY: 0.0792 AC XY: 5897 AN XY: 74442

African (AFR) AF: 0.0829 AC: 3445 AN: 41536

American (AMR) AF: 0.0856 AC: 1308 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0861 AC: 299 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.0350 AC: 169 AN: 4826

European-Finnish (FIN) AF: 0.0447 AC: 474 AN: 10612

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6820 AN: 68008

Other (OTH) AF: 0.0982 AC: 207 AN: 2108

Alfa AF: 0.0891 Hom.: 78

Bravo AF: 0.0880

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.57
DANN	Benign	0.43
PhyloP100		-0.83
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: rs4699699; hg19: chr4-99997179;