rs6836440

chr4-99127355-G-Achr4-99127355-G-Cchr4-99127355-G-T

Variant summary

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

The NM_000670.5(ADH4):c.844-11C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.97 in 1,582,896 control chromosomes in the GnomAD database, including 744,486 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 0.96 (70031 hom., cov: 32)
  • Exomes 𝑓: 0.97 (674455 hom.)
• Consequence: ADH4 NM_000670.5 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002529
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.726

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH4	NM_000670.5	c.844-11C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000265512.12
LOC100507053	NR_037884.1	n.429-6200G>A		intron_variant, non_coding_transcript_variant
ADH4	NM_001306171.2	c.901-11C>T		splice_polypyrimidine_tract_variant, intron_variant
ADH4	NM_001306172.2	c.901-11C>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH4	ENST00000265512.12	c.844-11C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000670.5	P1
	ENST00000500358.6	n.429-6200G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.959 AC: 145906 AN: 152154 Hom.: 69981 Cov.: 32

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.956

Gnomad ASJ AF: 0.973

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.979

Gnomad FIN AF: 0.944

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.968

GnomAD3 exomes AF: 0.964 AC: 222815 AN: 231060 Hom.: 107505 AF XY: 0.968 AC XY: 120761 AN XY: 124758

Gnomad AFR exome AF: 0.929

Gnomad AMR exome AF: 0.931

Gnomad ASJ exome AF: 0.979

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.981

Gnomad FIN exome AF: 0.941

Gnomad NFE exome AF: 0.972

Gnomad OTH exome AF: 0.966

GnomAD4 exome AF: 0.971 AC: 1388970 AN: 1430624 Hom.: 674455 Cov.: 32 AF XY: 0.971 AC XY: 691076 AN XY: 711358

Gnomad4 AFR exome AF: 0.930

Gnomad4 AMR exome AF: 0.932

Gnomad4 ASJ exome AF: 0.978

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.982

Gnomad4 FIN exome AF: 0.941

Gnomad4 NFE exome AF: 0.973

Gnomad4 OTH exome AF: 0.972

GnomAD4 genome AF: 0.959 AC: 146015 AN: 152272 Hom.: 70031 Cov.: 32 AF XY: 0.959 AC XY: 71404 AN XY: 74436

Gnomad4 AFR AF: 0.934

Gnomad4 AMR AF: 0.956

Gnomad4 ASJ AF: 0.973

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.979

Gnomad4 FIN AF: 0.944

Gnomad4 NFE AF: 0.971

Gnomad4 OTH AF: 0.968

Alfa AF: 0.964 Hom.: 23524

Bravo AF: 0.957

Asia WGS AF: 0.977 AC: 3399 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	7.3
Dann	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.0
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: rs6836440; hg19: chr4-100048506;