20-38882760-A-G

Position:

• chr20-38882760-A-G

Variant summary

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

The NM_015568.4(PPP1R16B):​c.251-6835A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 152,052 control chromosomes in the GnomAD database, including 40,305 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 0.72 (40305 hom., cov: 31)
• Consequence: PPP1R16B NM_015568.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140

Genes affected

PPP1R16B (HGNC:15850): (protein phosphatase 1 regulatory subunit 16B) The protein encoded by this gene is membrane-associated and contains five ankyrin repeats, a protein phosphatase-1-interacting domain, and a carboxy-terminal CAAX box domain. Synthesis of the encoded protein is inhibited by transforming growth factor beta-1. The protein may bind to the membrane through its CAAX box domain and may act as a signaling molecule through interaction with protein phosphatase-1. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate mature protein. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R16B	NM_015568.4	c.251-6835A>G		intron_variant		ENST00000299824.6	NP_056383.1
PPP1R16B	XM_011528768.4	c.-519A>G		5_prime_UTR_variant	1/10		XP_011527070.1
PPP1R16B	NM_001172735.3	c.251-6835A>G		intron_variant			NP_001166206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R16B	ENST00000299824.6	c.251-6835A>G		intron_variant		1	NM_015568.4	ENSP00000299824	P1
PPP1R16B	ENST00000373331.2	c.251-6835A>G		intron_variant		5		ENSP00000362428
PPP1R16B	ENST00000463749.1	n.64-6835A>G		intron_variant, non_coding_transcript_variant		2
PPP1R16B	ENST00000468265.5	n.147-6835A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110092 AN: 151934 Hom.: 40259 Cov.: 31

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.720

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

GnomAD4 genome AF: 0.725 AC: 110195 AN: 152052 Hom.: 40305 Cov.: 31 AF XY: 0.723 AC XY: 53706 AN XY: 74294

Gnomad4 AFR AF: 0.740

Gnomad4 AMR AF: 0.725

Gnomad4 ASJ AF: 0.672

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.847

Gnomad4 FIN AF: 0.695

Gnomad4 NFE AF: 0.739

Gnomad4 OTH AF: 0.713

Alfa AF: 0.732 Hom.: 16418

Bravo AF: 0.717

Asia WGS AF: 0.646 AC: 2248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.0
DANN	Benign	0.39

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: rs208799; hg19: chr20-37511403;