chr3-52227015-A-G

Variant names:

• chr3-52227015-A-G
• rs187084
• ENST00000494383.1:c.462+2646T>C

Variant summary

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

The ENST00000494383.1(ENSG00000173366):​c.462+2646T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,132 control chromosomes in the GnomAD database, including 11,169 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 0.38 (11169 hom., cov: 33)
• Consequence: ENSG00000173366 ENST00000494383.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.477
• Publications: 383 publications found

Genes affected

ENSG00000173366 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.421 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
ENSG00000173366	ENST00000494383.1	c.462+2646T>C		intron_variant	Intron 4 of 4	2		ENSP00000417517.1
ENSG00000173366	ENST00000478201.1	n.112-1380T>C		intron_variant	Intron 1 of 2	2		ENSP00000419980.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57423 AN: 152014 Hom.: 11156 Cov.: 33

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.378 AC: 57464 AN: 152132 Hom.: 11169 Cov.: 33 AF XY: 0.379 AC XY: 28156 AN XY: 74384

African (AFR) AF: 0.302 AC: 12517 AN: 41500

American (AMR) AF: 0.429 AC: 6567 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1417 AN: 3470

East Asian (EAS) AF: 0.393 AC: 2033 AN: 5168

South Asian (SAS) AF: 0.351 AC: 1692 AN: 4826

European-Finnish (FIN) AF: 0.422 AC: 4465 AN: 10570

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.404 AC: 27465 AN: 67984

Other (OTH) AF: 0.369 AC: 780 AN: 2116

Alfa AF: 0.399 Hom.: 32142

Bravo AF: 0.375

Asia WGS AF: 0.395 AC: 1373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.94
DANN	Benign	0.36
PhyloP100		-0.48
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: rs187084; hg19: chr3-52261031;