10-37679350-A-G

Variant names:

• chr10-37679350-A-G
• rs289647
• XR_930828.2:n.479+2T>C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PVS1_Moderate BA1

The XR_930828.2(LOC105376498):​n.479+2T>C variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 152,092 control chromosomes in the GnomAD database, including 17,193 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 0.47 (17193 hom., cov: 33)
• Consequence: LOC105376498 XR_930828.2 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.67

Genes affected

LOC105376498 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105376498	XR_930828.2	n.479+2T>C		splice_donor_variant, intron_variant	Intron 2 of 3
LOC105376498	XR_930829.2	n.414+545T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71496 AN: 151972 Hom.: 17155 Cov.: 33

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.497

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

GnomAD4 genome AF: 0.471 AC: 71586 AN: 152092 Hom.: 17193 Cov.: 33 AF XY: 0.464 AC XY: 34466 AN XY: 74356

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.495

Alfa AF: 0.488 Hom.: 9672

Bravo AF: 0.492

Asia WGS AF: 0.473 AC: 1645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.81
DANN	Benign	0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs289647; hg19: chr10-37968278;