chr20-38848391-T-C

Position:

• chr20-38848391-T-C

Variant summary

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

The NM_015568.4(PPP1R16B):​c.250+12216T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 152,094 control chromosomes in the GnomAD database, including 34,069 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 0.66 (34069 hom., cov: 32)
• Consequence: PPP1R16B NM_015568.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R16B	NM_015568.4	c.250+12216T>C		intron_variant		ENST00000299824.6	NP_056383.1
PPP1R16B	NM_001172735.3	c.250+12216T>C		intron_variant			NP_001166206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R16B	ENST00000299824.6	c.250+12216T>C		intron_variant		1	NM_015568.4	ENSP00000299824	P1
PPP1R16B	ENST00000373331.2	c.250+12216T>C		intron_variant		5		ENSP00000362428
PPP1R16B	ENST00000463749.1	n.63+9881T>C		intron_variant, non_coding_transcript_variant		2
PPP1R16B	ENST00000468265.5	n.146+10193T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101078 AN: 151976 Hom.: 34065 Cov.: 32

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.665 AC: 101131 AN: 152094 Hom.: 34069 Cov.: 32 AF XY: 0.665 AC XY: 49407 AN XY: 74326

Gnomad4 AFR AF: 0.771

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.680

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.615

Gnomad4 OTH AF: 0.647

Alfa AF: 0.661 Hom.: 4809

Bravo AF: 0.668

Asia WGS AF: 0.666 AC: 2316 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.23
DANN	Benign	0.52

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: rs6028163; hg19: chr20-37477034;