rs12486865

Variant names:

• chr3-100237712-G-C
• rs12486865
• ENST00000654821.1:n.195+22358C>G

Variant summary

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

The ENST00000654821.1(ENSG00000287378):​n.195+22358C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 151,536 control chromosomes in the GnomAD database, including 5,988 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 0.27 (5988 hom., cov: 30)
• Consequence: ENSG00000287378 ENST00000654821.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.358
• Publications: 4 publications found

Genes affected

ENSG00000287378 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 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
ENSG00000287378	ENST00000654821.1	n.195+22358C>G		intron_variant	Intron 1 of 3
ENSG00000287378	ENST00000800905.1	n.193+22358C>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41566 AN: 151420 Hom.: 5987 Cov.: 30

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.0831

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.274 AC: 41580 AN: 151536 Hom.: 5988 Cov.: 30 AF XY: 0.270 AC XY: 19958 AN XY: 74018

African (AFR) AF: 0.247 AC: 10214 AN: 41282

American (AMR) AF: 0.262 AC: 3996 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1145 AN: 3468

East Asian (EAS) AF: 0.0827 AC: 427 AN: 5162

South Asian (SAS) AF: 0.263 AC: 1261 AN: 4794

European-Finnish (FIN) AF: 0.232 AC: 2424 AN: 10430

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21232 AN: 67870

Other (OTH) AF: 0.288 AC: 605 AN: 2100

Alfa AF: 0.283 Hom.: 783

Bravo AF: 0.274

Asia WGS AF: 0.180 AC: 625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.0
DANN	Benign	0.53
PhyloP100		0.36

Splicing

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

Other links and lift over

dbSNP: rs12486865; hg19: chr3-99956556;