ENST00000559246.1:n.74+11277G>A

Variant names:

• chr15-35158348-C-T
• rs11854468
• ENST00000559246.1:n.74+11277G>A

Variant summary

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

The ENST00000559246.1(ENSG00000259336):​n.74+11277G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,080 control chromosomes in the GnomAD database, including 1,392 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 0.12 (1392 hom., cov: 33)
• Consequence: ENSG00000259336 ENST00000559246.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340
• Publications: 7 publications found

Genes affected

ENSG00000259336 (HGNC:):

DPH6 (HGNC:30543): (diphthamine biosynthesis 6) Enables diphthine-ammonia ligase activity. Predicted to be involved in peptidyl-diphthamide biosynthetic process from peptidyl-histidine. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000559246.1. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000259336	ENST00000559246.1	TSL:5	n.74+11277G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18436 AN: 151962 Hom.: 1389 Cov.: 33

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0929

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0824

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0878

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.121 AC: 18462 AN: 152080 Hom.: 1392 Cov.: 33 AF XY: 0.118 AC XY: 8779 AN XY: 74348

African (AFR) AF: 0.207 AC: 8570 AN: 41476

American (AMR) AF: 0.0928 AC: 1416 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 677 AN: 3470

East Asian (EAS) AF: 0.00271 AC: 14 AN: 5174

South Asian (SAS) AF: 0.125 AC: 603 AN: 4828

European-Finnish (FIN) AF: 0.0824 AC: 873 AN: 10598

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.0878 AC: 5967 AN: 67960

Other (OTH) AF: 0.126 AC: 266 AN: 2112

Alfa AF: 0.102 Hom.: 1385

Bravo AF: 0.125

Asia WGS AF: 0.0670 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.8
DANN	Benign	0.37
PhyloP100		-0.034
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs11854468; hg19: chr15-35450549;