rs75076193

Variant names:

• chr7-143139553-C-T
• rs75076193
• NM_002652.3:c.352C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-143139553-C-T
• chr7-143139553-C-A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_002652.3(PIP):​c.352C>T​(p.Arg118Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00829 in 1,612,766 control chromosomes in the GnomAD database, including 217 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0068 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0084 (207 hom.)
• Consequence: PIP NM_002652.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.66
• Publications: 6 publications found

Genes affected

PIP (HGNC:8993): (prolactin induced protein) Enables IgG binding activity; aspartic-type endopeptidase activity; and identical protein binding activity. Involved in several processes, including detection of chemical stimulus involved in sensory perception of bitter taste; negative regulation of T cell apoptotic process; and proteolysis. Located in extracellular space and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00939703).
• BP6: Variant 7-143139553-C-T is Benign according to our data. Variant chr7-143139553-C-T is described in ClinVar as Benign. ClinVar VariationId is 731154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002652.3. 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
	PIP	NM_002652.3	MANE Select	c.352C>T	p.Arg118Trp	missense	Exon 4 of 4	NP_002643.1	P12273

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP	ENST00000291009.4	TSL:1 MANE Select	c.352C>T	p.Arg118Trp	missense	Exon 4 of 4	ENSP00000291009.3	P12273

Frequencies

GnomAD3 genomes AF: 0.00683 AC: 1038 AN: 152000 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00923

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0235

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00899

Gnomad OTH AF: 0.00720

GnomAD2 exomes AF: 0.00732 AC: 1841 AN: 251432 AF XY: 0.00712

Gnomad AFR exome AF: 0.00172

Gnomad AMR exome AF: 0.00205

Gnomad ASJ exome AF: 0.00655

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0240

Gnomad NFE exome AF: 0.00947

Gnomad OTH exome AF: 0.00847

GnomAD4 exome AF: 0.00844 AC: 12333 AN: 1460648 Hom.: 207 Cov.: 31 AF XY: 0.00812 AC XY: 5904 AN XY: 726666

African (AFR) AF: 0.00158 AC: 53 AN: 33478

American (AMR) AF: 0.00250 AC: 112 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00728 AC: 190 AN: 26102

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39698

South Asian (SAS) AF: 0.000812 AC: 70 AN: 86254

European-Finnish (FIN) AF: 0.0234 AC: 1248 AN: 53420

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5764

European-Non Finnish (NFE) AF: 0.00919 AC: 10208 AN: 1110864

Other (OTH) AF: 0.00724 AC: 437 AN: 60348

GnomAD4 genome AF: 0.00682 AC: 1038 AN: 152118 Hom.: 10 Cov.: 32 AF XY: 0.00725 AC XY: 539 AN XY: 74374

African (AFR) AF: 0.00147 AC: 61 AN: 41520

American (AMR) AF: 0.00419 AC: 64 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00923 AC: 32 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4816

European-Finnish (FIN) AF: 0.0235 AC: 249 AN: 10578

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00899 AC: 611 AN: 67958

Other (OTH) AF: 0.00712 AC: 15 AN: 2106

Alfa AF: 0.00814 Hom.: 46

Bravo AF: 0.00546

TwinsUK AF: 0.00998 AC: 37

ALSPAC AF: 0.00960 AC: 37

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.00942 AC: 81

ExAC AF: 0.00754 AC: 916

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00791

EpiControl AF: 0.00854

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.94
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0094	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.5	L
PhyloP100		-1.7
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.097
Sift	Benign	0.050	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.19
MVP		0.34
MPC		0.34
ClinPred		0.068	T
GERP RS		-4.8
Varity_R		0.41
gMVP		0.23
Mutation Taster		=99/1	polymorphism

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: rs75076193; hg19: chr7-142836646;