1-43547684-G-A

Variant names:

• chr1-43547684-G-A
• rs2782641
• NM_002840.5:c.91+2518G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002840.5(PTPRF):​c.91+2518G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 152,194 control chromosomes in the GnomAD database, including 33,106 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 0.66 (33106 hom., cov: 33)
• Consequence: PTPRF NM_002840.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.657
• Publications: 21 publications found

Genes affected

PTPRF (HGNC:9670): (protein tyrosine phosphatase receptor type F) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region, a single transmembrane region, and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains three Ig-like domains, and nine non-Ig like domains similar to that of neural-cell adhesion molecule. This PTP was shown to function in the regulation of epithelial cell-cell contacts at adherents junctions, as well as in the control of beta-catenin signaling. An increased expression level of this protein was found in the insulin-responsive tissue of obese, insulin-resistant individuals, and may contribute to the pathogenesis of insulin resistance. Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported. [provided by RefSeq, Jul 2008]

PTPRF Gene-Disease associations (from GenCC):

• breasts and/or nipples, aplasia or hypoplasia of, 2

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002840.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRF	NM_002840.5	MANE Select	c.91+2518G>A		intron	N/A	NP_002831.2
	PTPRF	NM_130440.4		c.91+2518G>A		intron	N/A	NP_569707.2
	PTPRF	NM_001329138.2		c.91+2518G>A		intron	N/A	NP_001316067.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRF	ENST00000359947.9	TSL:1 MANE Select	c.91+2518G>A		intron	N/A	ENSP00000353030.4
	PTPRF	ENST00000438120.5	TSL:1	c.91+2518G>A		intron	N/A	ENSP00000398822.1
	PTPRF	ENST00000437607.1	TSL:1	c.91+2518G>A		intron	N/A	ENSP00000413306.1

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99943 AN: 152076 Hom.: 33089 Cov.: 33

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.657 AC: 100008 AN: 152194 Hom.: 33106 Cov.: 33 AF XY: 0.661 AC XY: 49204 AN XY: 74412

African (AFR) AF: 0.686 AC: 28486 AN: 41532

American (AMR) AF: 0.687 AC: 10507 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2262 AN: 3472

East Asian (EAS) AF: 0.767 AC: 3964 AN: 5168

South Asian (SAS) AF: 0.833 AC: 4019 AN: 4822

European-Finnish (FIN) AF: 0.621 AC: 6581 AN: 10598

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.620 AC: 42127 AN: 67986

Other (OTH) AF: 0.631 AC: 1336 AN: 2116

Alfa AF: 0.632 Hom.: 40205

Bravo AF: 0.661

Asia WGS AF: 0.801 AC: 2786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Benign	0.84
PhyloP100		0.66
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2782641; hg19: chr1-44013355;