4-54228348-C-A

Variant names:

• chr4-54228348-C-A
• rs1135534
• ENST00000507166.5:c.1018-46577C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000507166.5(ENSG00000282278):​c.1018-46577C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.035 in 152,270 control chromosomes in the GnomAD database, including 144 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 0.035 (144 hom., cov: 32)
• Consequence: ENSG00000282278 ENST00000507166.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 1 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=-0.76).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.035 (5334/152270) while in subpopulation NFE AF = 0.0415 (2823/68024). AF 95% confidence interval is 0.0402. There are 144 homozygotes in GnomAd4. There are 2762 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 144 gene

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.1018-46577C>A		intron_variant	Intron 12 of 23	2		ENSP00000423325.1

Frequencies

GnomAD3 genomes AF: 0.0351 AC: 5335 AN: 152152 Hom.: 144 Cov.: 32

Gnomad AFR AF: 0.00671

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.0396

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0835

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0415

Gnomad OTH AF: 0.0425

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

GnomAD4 genome AF: 0.0350 AC: 5334 AN: 152270 Hom.: 144 Cov.: 32 AF XY: 0.0371 AC XY: 2762 AN XY: 74458

African (AFR) AF: 0.00669 AC: 278 AN: 41570

American (AMR) AF: 0.0395 AC: 604 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 417 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.0120 AC: 58 AN: 4830

European-Finnish (FIN) AF: 0.0835 AC: 886 AN: 10606

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0415 AC: 2823 AN: 68024

Other (OTH) AF: 0.0416 AC: 88 AN: 2114

Alfa AF: 0.0279 Hom.: 65

Bravo AF: 0.0316

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.3
DANN	Benign	0.80
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism

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: rs1135534; hg19: chr4-55094515;