11-67435917-C-T

Variant names:

• chr11-67435917-C-T
• rs141177910
• NM_005608.3:c.437G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_005608.3(PTPRCAP):​c.437G>A​(p.Arg146Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,612,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00060 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: PTPRCAP NM_005608.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.401

Genes affected

PTPRCAP (HGNC:9667): (protein tyrosine phosphatase receptor type C associated protein) The protein encoded by this gene was identified as a transmembrane phosphoprotein specifically associated with tyrosine phosphatase PTPRC/CD45, a key regulator of T- and B-lymphocyte activation. The interaction with PTPRC may be required for the stable expression of this protein. [provided by RefSeq, Jul 2008]

CORO1B (HGNC:2253): (coronin 1B) Members of the coronin family, such as CORO1B, are WD repeat-containing actin-binding proteins that regulate cell motility (Cai et al., 2005 [PubMed 16027158]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0069185197).
• BP6: Variant 11-67435917-C-T is Benign according to our data. Variant chr11-67435917-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2407360.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRCAP	NM_005608.3	c.437G>A	p.Arg146Gln	missense_variant	Exon 2 of 2	ENST00000326294.4	NP_005599.1
CORO1B	NM_020441.3	c.*2459G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000341356.10	NP_065174.1
CORO1B	NM_001018070.3	c.*2459G>A		3_prime_UTR_variant	Exon 12 of 12		NP_001018080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRCAP	ENST00000326294.4	c.437G>A	p.Arg146Gln	missense_variant	Exon 2 of 2	1	NM_005608.3	ENSP00000325589.3
CORO1B	ENST00000341356	c.*2459G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_020441.3	ENSP00000340211.5
CORO1B	ENST00000616321.4	n.*3191G>A		non_coding_transcript_exon_variant	Exon 11 of 11	2		ENSP00000479949.1
CORO1B	ENST00000616321.4	n.*3191G>A		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000479949.1

Frequencies

GnomAD3 genomes AF: 0.000591 AC: 90 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000204 AC: 51 AN: 249662 Hom.: 0 AF XY: 0.000177 AC XY: 24 AN XY: 135236

Gnomad AFR exome AF: 0.00179

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.000160

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000103 AC: 150 AN: 1460588 Hom.: 0 Cov.: 31 AF XY: 0.0000826 AC XY: 60 AN XY: 726610

Gnomad4 AFR exome AF: 0.00176

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0000190

Gnomad4 NFE exome AF: 0.0000648

Gnomad4 OTH exome AF: 0.000282

GnomAD4 genome AF: 0.000598 AC: 91 AN: 152274 Hom.: 0 Cov.: 32 AF XY: 0.000484 AC XY: 36 AN XY: 74454

Gnomad4 AFR AF: 0.00197

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000144 Hom.: 0

Bravo AF: 0.000688

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000272 AC: 33

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 03, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.54
DANN	Benign	0.82
DEOGEN2	Benign	0.050	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.0069	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.0030
Sift	Benign	0.54	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.043
MVP		0.068
MPC		0.31
ClinPred		0.0022	T
GERP RS		-3.3
Varity_R		0.018
gMVP		0.022

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: rs141177910; hg19: chr11-67203388;