ENST00000507391.1:n.147+2C>T

Variant names:

• chr5-146401129-C-T
• rs2304066
• ENST00000507391.1:n.147+2C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PVS1_Moderate BA1

The ENST00000507391.1(ENSG00000248842):​n.147+2C>T variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 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: ENSG00000248842 ENST00000507391.1 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164
• Publications: 4 publications found

Genes affected

ENSG00000248842 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene. Cryptic splice site detected, with MaxEntScore 10, offset of 0 (no position change), new splice context is: acgGTaagg. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000248842	ENST00000507391.1	n.147+2C>T		splice_donor_variant, intron_variant	Intron 1 of 1	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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.667 AC: 4 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.850 AC: 17 AN: 20

Other (OTH) AF: 0.667 AC: 4 AN: 6

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

African (AFR) AF: 0.568 AC: 23504 AN: 41414

American (AMR) AF: 0.769 AC: 11767 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2826 AN: 3468

East Asian (EAS) AF: 0.594 AC: 3064 AN: 5154

South Asian (SAS) AF: 0.858 AC: 4129 AN: 4810

European-Finnish (FIN) AF: 0.769 AC: 8133 AN: 10570

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52711 AN: 67982

Other (OTH) AF: 0.729 AC: 1533 AN: 2102

Alfa AF: 0.763 Hom.: 38369

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
PhyloP100		-0.16

Splicing

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

Other links and lift over

dbSNP: rs2304066; hg19: chr5-145780692;