chr16-19874418-C-G

Position:

• chr16-19874418-C-G

Variant summary

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

The NM_016235.3(GPRC5B):​c.-1-1572G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,054 control chromosomes in the GnomAD database, including 9,320 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 0.35 (9320 hom., cov: 32)
• Consequence: GPRC5B NM_016235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374

Genes affected

GPRC5B (HGNC:13308): (G protein-coupled receptor class C group 5 member B) This gene encodes a member of the type 3 G protein-coupled receptor family. Members of this superfamily are characterized by a signature 7-transmembrane domain motif. The encoded protein may modulate insulin secretion and increased protein expression is associated with type 2 diabetes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPRC5B	NM_016235.3	c.-1-1572G>C		intron_variant		ENST00000300571.7	NP_057319.1
GPRC5B	NM_001304771.1	c.393-1572G>C		intron_variant			NP_001291700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPRC5B	ENST00000300571.7	c.-1-1572G>C		intron_variant		1	NM_016235.3	ENSP00000300571	P1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52811 AN: 151934 Hom.: 9318 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.347 AC: 52825 AN: 152054 Hom.: 9320 Cov.: 32 AF XY: 0.343 AC XY: 25509 AN XY: 74310

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.351

Alfa AF: 0.189 Hom.: 374

Bravo AF: 0.353

Asia WGS AF: 0.226 AC: 786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.81
DANN	Benign	0.57

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: rs724615; hg19: chr16-19885740;