7-143138146-A-G

Position:

• chr7-143138146-A-G

Variant summary

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

The NM_002652.3(PIP):​c.202-929A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,042 control chromosomes in the GnomAD database, including 1,735 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 0.12 (1735 hom., cov: 32)
• Consequence: PIP NM_002652.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIP	NM_002652.3	c.202-929A>G		intron_variant		ENST00000291009.4	NP_002643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIP	ENST00000291009.4	c.202-929A>G		intron_variant		1	NM_002652.3	ENSP00000291009.3

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18286 AN: 151924 Hom.: 1731 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0940

Gnomad ASJ AF: 0.0612

Gnomad EAS AF: 0.0352

Gnomad SAS AF: 0.0742

Gnomad FIN AF: 0.0234

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0755

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.120 AC: 18312 AN: 152042 Hom.: 1735 Cov.: 32 AF XY: 0.117 AC XY: 8680 AN XY: 74340

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.0938

Gnomad4 ASJ AF: 0.0612

Gnomad4 EAS AF: 0.0353

Gnomad4 SAS AF: 0.0749

Gnomad4 FIN AF: 0.0234

Gnomad4 NFE AF: 0.0755

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0813 Hom.: 1514

Bravo AF: 0.133

Asia WGS AF: 0.0730 AC: 255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.50

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: rs9986765; hg19: chr7-142835239;