rs2304066

Positions:

• chr5-146401129-C-T

Variant summary

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

The ENST00000507391.1(ENSG00000248842):​n.147+2C>T variant causes a splice donor, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 152,042 control chromosomes in the GnomAD database, including 39,409 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 0.71 (39400 hom., cov: 31)
  • Exomes 𝑓: 0.76 (9 hom.)
• Consequence: ENST00000507391.1 splice_donor, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164

Genes affected

(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 = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000507391.1	n.147+2C>T		splice_donor_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108328 AN: 151890 Hom.: 39378 Cov.: 31

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.858

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.727

GnomAD4 exome AF: 0.765 AC: 26 AN: 34 Hom.: 9 Cov.: 0 AF XY: 0.750 AC XY: 15 AN XY: 20

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.850

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.713 AC: 108391 AN: 152008 Hom.: 39400 Cov.: 31 AF XY: 0.716 AC XY: 53241 AN XY: 74324

Gnomad4 AFR AF: 0.568

Gnomad4 AMR AF: 0.769

Gnomad4 ASJ AF: 0.815

Gnomad4 EAS AF: 0.594

Gnomad4 SAS AF: 0.858

Gnomad4 FIN AF: 0.769

Gnomad4 NFE AF: 0.775

Gnomad4 OTH AF: 0.729

Alfa AF: 0.766 Hom.: 27316

Bravo AF: 0.700

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.0
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: rs2304066; hg19: chr5-145780692;