ENST00000457561.3:n.184+34181T>A

Variant names:

• chr6-58077708-T-A
• rs9500270
• ENST00000457561.3:n.184+34181T>A

Variant summary

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

The ENST00000457561.3(ENSG00000225096):​n.184+34181T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0213 in 152,226 control chromosomes in the GnomAD database, including 50 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 0.021 (50 hom., cov: 33)
• Consequence: ENSG00000225096 ENST00000457561.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.888
• Publications: 1 publications found

Genes affected

ENSG00000225096 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0213 (3243/152226) while in subpopulation AFR AF = 0.0454 (1886/41502). AF 95% confidence interval is 0.0437. There are 50 homozygotes in GnomAd4. There are 1509 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 50 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
ENSG00000225096	ENST00000457561.3	n.184+34181T>A		intron_variant	Intron 2 of 3	5
ENSG00000225096	ENST00000641631.1	n.150+34181T>A		intron_variant	Intron 2 of 6
ENSG00000225096	ENST00000641775.1	n.316+34181T>A		intron_variant	Intron 3 of 5

Frequencies

GnomAD3 genomes AF: 0.0212 AC: 3231 AN: 152108 Hom.: 47 Cov.: 33

Gnomad AFR AF: 0.0452

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0138

Gnomad ASJ AF: 0.0548

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0119

Gnomad OTH AF: 0.0234

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

GnomAD4 genome AF: 0.0213 AC: 3243 AN: 152226 Hom.: 50 Cov.: 33 AF XY: 0.0203 AC XY: 1509 AN XY: 74416

African (AFR) AF: 0.0454 AC: 1886 AN: 41502

American (AMR) AF: 0.0137 AC: 210 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0548 AC: 190 AN: 3470

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5184

South Asian (SAS) AF: 0.0106 AC: 51 AN: 4828

European-Finnish (FIN) AF: 0.00217 AC: 23 AN: 10600

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0118 AC: 806 AN: 68030

Other (OTH) AF: 0.0232 AC: 49 AN: 2112

Alfa AF: 0.0177 Hom.: 6

Bravo AF: 0.0239

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.51
PhyloP100		0.89

Splicing

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

Other links and lift over

dbSNP: rs9500270; hg19: chr6-58403986;