4-54226459-T-C

Variant names:

• chr4-54226459-T-C
• rs2114039
• ENST00000507166.5:c.1018-48466T>C

Variant summary

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

The ENST00000507166.5(ENSG00000282278):​c.1018-48466T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 151,950 control chromosomes in the GnomAD database, including 13,988 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 0.39 (13988 hom., cov: 32)
• Consequence: ENSG00000282278 ENST00000507166.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356
• Publications: 30 publications found

Genes affected

ENSG00000282278 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000282278	ENST00000507166.5	c.1018-48466T>C		intron_variant	Intron 12 of 23	2		ENSP00000423325.1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59733 AN: 151832 Hom.: 13937 Cov.: 32

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.394 AC: 59848 AN: 151950 Hom.: 13988 Cov.: 32 AF XY: 0.392 AC XY: 29100 AN XY: 74260

African (AFR) AF: 0.661 AC: 27396 AN: 41432

American (AMR) AF: 0.409 AC: 6251 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 657 AN: 3466

East Asian (EAS) AF: 0.292 AC: 1501 AN: 5142

South Asian (SAS) AF: 0.274 AC: 1317 AN: 4806

European-Finnish (FIN) AF: 0.273 AC: 2876 AN: 10552

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18821 AN: 67960

Other (OTH) AF: 0.347 AC: 733 AN: 2114

Alfa AF: 0.309 Hom.: 33768

Bravo AF: 0.417

Asia WGS AF: 0.344 AC: 1196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.2
DANN	Benign	0.59
PhyloP100		0.36
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: rs2114039; hg19: chr4-55092626;