1-96779490-A-G

Position:

• chr1-96779490-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021190.4(PTBP2):​c.708+1544A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0949 in 152,144 control chromosomes in the GnomAD database, including 939 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 0.095 (939 hom., cov: 32)
• Consequence: PTBP2 NM_021190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.812

Genes affected

PTBP2 (HGNC:17662): (polypyrimidine tract binding protein 2) The protein encoded by this gene binds to intronic polypyrimidine clusters in pre-mRNA molecules and is implicated in controlling the assembly of other splicing-regulatory proteins. This protein is very similar to the polypyrimidine tract binding protein (PTB) but most of its isoforms are expressed primarily in the brain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTBP2	NM_021190.4	c.708+1544A>G		intron_variant		ENST00000674951.1	NP_067013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTBP2	ENST00000674951.1	c.708+1544A>G		intron_variant			NM_021190.4	ENSP00000502818	A1

Frequencies

GnomAD3 genomes AF: 0.0949 AC: 14433 AN: 152026 Hom.: 939 Cov.: 32

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.0584

Gnomad ASJ AF: 0.0813

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0543

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.0796

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

GnomAD4 genome AF: 0.0949 AC: 14432 AN: 152144 Hom.: 939 Cov.: 32 AF XY: 0.0936 AC XY: 6959 AN XY: 74386

Gnomad4 AFR AF: 0.0257

Gnomad4 AMR AF: 0.0583

Gnomad4 ASJ AF: 0.0813

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0548

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.0792

Alfa AF: 0.0951 Hom.: 332

Bravo AF: 0.0812

Asia WGS AF: 0.0210 AC: 73 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10489798; hg19: chr1-97245046;