rs11660158

Variant names:

• chr18-8116627-A-G
• rs11660158
• NM_001105244.2:c.2167+1800A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001105244.2(PTPRM):​c.2167+1800A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,230 control chromosomes in the GnomAD database, including 2,621 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 0.18 (2621 hom., cov: 33)
• Consequence: PTPRM NM_001105244.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 7 publications found

Genes affected

PTPRM (HGNC:9675): (protein tyrosine phosphatase receptor type M) 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 catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains a meprin-A5 antigen-PTP mu (MAM) domain, an Ig-like domain and four fibronectin type III-like repeats. This PTP has been shown to mediate cell-cell aggregation through the interaction with another molecule of this PTP on an adjacent cell. This PTP can interact with scaffolding protein RACK1/GNB2L1, which may be necessary for the downstream signaling in response to cell-cell adhesion. Alternative splicing results in multiple transcripts encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105244.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRM	NM_001105244.2	MANE Select	c.2167+1800A>G		intron	N/A	NP_001098714.1	P28827-2
	PTPRM	NM_002845.4		c.2167+1800A>G		intron	N/A	NP_002836.3
	PTPRM	NM_001378147.1		c.1528+1800A>G		intron	N/A	NP_001365076.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRM	ENST00000580170.6	TSL:1 MANE Select	c.2167+1800A>G		intron	N/A	ENSP00000463325.1	P28827-2
	PTPRM	ENST00000332175.12	TSL:1	c.2167+1800A>G		intron	N/A	ENSP00000331418.8	P28827-1
	PTPRM	ENST00000400053.8	TSL:5	c.1981+1800A>G		intron	N/A	ENSP00000382927.4	E7EPS8

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27108 AN: 152110 Hom.: 2619 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.0424

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.178 AC: 27117 AN: 152230 Hom.: 2621 Cov.: 33 AF XY: 0.172 AC XY: 12827 AN XY: 74420

African (AFR) AF: 0.125 AC: 5204 AN: 41546

American (AMR) AF: 0.166 AC: 2535 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 891 AN: 3472

East Asian (EAS) AF: 0.0419 AC: 217 AN: 5182

South Asian (SAS) AF: 0.133 AC: 640 AN: 4816

European-Finnish (FIN) AF: 0.168 AC: 1777 AN: 10600

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15145 AN: 68006

Other (OTH) AF: 0.194 AC: 410 AN: 2114

Alfa AF: 0.205 Hom.: 3930

Bravo AF: 0.177

Asia WGS AF: 0.0730 AC: 253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		1.1
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: rs11660158; hg19: chr18-8116625;