15-96062683-C-T

Position:

• chr15-96062683-C-T

Variant summary

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

The ENST00000648034.1(ENSG00000259702):​n.154+1G>A variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,058 control chromosomes in the GnomAD database, including 2,019 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 0.16 (2019 hom., cov: 32)
• Consequence: ENSG00000259702 ENST00000648034.1 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

Genes affected

ENSG00000259702 (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 (SAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC112268156	XR_002957737.1	n.450+71799C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000259702	ENST00000558860.2	n.81+1594G>A		intron_variant		4
ENSG00000275443	ENST00000619812.1	n.303+71799C>T		intron_variant		5
ENSG00000259702	ENST00000648034.1	n.154+1G>A		splice_donor_variant, intron_variant

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24250 AN: 151942 Hom.: 2015 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.160 AC: 24264 AN: 152058 Hom.: 2019 Cov.: 32 AF XY: 0.162 AC XY: 12027 AN XY: 74332

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.145

Alfa AF: 0.103 Hom.: 227

Bravo AF: 0.154

Asia WGS AF: 0.169 AC: 587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.46
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11636705; hg19: chr15-96605912;