rs10519866

Variant names:

• chr4-147081922-T-C
• rs10519866
• ENST00000667105.1:n.515+8696T>C

Variant summary

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

The ENST00000667105.1(ENSG00000286371):​n.515+8696T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 152,138 control chromosomes in the GnomAD database, including 72 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 0.022 (72 hom., cov: 31)
• Consequence: ENSG00000286371 ENST00000667105.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162
• Publications: 0 publications found

Genes affected

ENSG00000286371 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0222 (3377/152138) while in subpopulation AFR AF = 0.0503 (2085/41490). AF 95% confidence interval is 0.0485. There are 72 homozygotes in GnomAd4. There are 1634 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 72 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105377476	XR_939316.3	n.352+8696T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000286371	ENST00000667105.1	n.515+8696T>C		intron_variant	Intron 3 of 3
ENSG00000286371	ENST00000671296.1	n.412+8696T>C		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0221 AC: 3366 AN: 152020 Hom.: 71 Cov.: 31

Gnomad AFR AF: 0.0500

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.00604

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.0177

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

GnomAD4 genome AF: 0.0222 AC: 3377 AN: 152138 Hom.: 72 Cov.: 31 AF XY: 0.0220 AC XY: 1634 AN XY: 74396

African (AFR) AF: 0.0503 AC: 2085 AN: 41490

American (AMR) AF: 0.0110 AC: 168 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.0284 AC: 137 AN: 4826

European-Finnish (FIN) AF: 0.00604 AC: 64 AN: 10602

Middle Eastern (MID) AF: 0.0377 AC: 11 AN: 292

European-Non Finnish (NFE) AF: 0.0124 AC: 842 AN: 67998

Other (OTH) AF: 0.0176 AC: 37 AN: 2108

Alfa AF: 0.0185 Hom.: 9

Bravo AF: 0.0226

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.31
PhyloP100		-0.16

Splicing

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

Other links and lift over

dbSNP: rs10519866; hg19: chr4-148003074;