16-19872963-C-T

Variant names:

• chr16-19872963-C-T
• rs2240047
• NM_016235.3:c.-1-117G>A

Variant summary

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

The NM_016235.3(GPRC5B):​c.-1-117G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 708,102 control chromosomes in the GnomAD database, including 163,599 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 0.69 (36945 hom., cov: 32)
  • Exomes 𝑓: 0.67 (126654 hom.)
• Consequence: GPRC5B NM_016235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPRC5B	NM_016235.3	c.-1-117G>A		intron_variant	Intron 1 of 3	ENST00000300571.7	NP_057319.1
GPRC5B	NM_001304771.1	c.393-117G>A		intron_variant	Intron 1 of 3		NP_001291700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPRC5B	ENST00000300571.7	c.-1-117G>A		intron_variant	Intron 1 of 3	1	NM_016235.3	ENSP00000300571.2

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105256 AN: 151944 Hom.: 36912 Cov.: 32

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.798

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.706

GnomAD4 exome AF: 0.670 AC: 372449 AN: 556040 Hom.: 126654 AF XY: 0.672 AC XY: 197564 AN XY: 294084

Gnomad4 AFR exome AF: 0.776

Gnomad4 AMR exome AF: 0.504

Gnomad4 ASJ exome AF: 0.786

Gnomad4 EAS exome AF: 0.868

Gnomad4 SAS exome AF: 0.687

Gnomad4 FIN exome AF: 0.608

Gnomad4 NFE exome AF: 0.655

Gnomad4 OTH exome AF: 0.682

GnomAD4 genome AF: 0.693 AC: 105333 AN: 152062 Hom.: 36945 Cov.: 32 AF XY: 0.692 AC XY: 51427 AN XY: 74322

Gnomad4 AFR AF: 0.778

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.798

Gnomad4 EAS AF: 0.851

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.709

Alfa AF: 0.667 Hom.: 6897

Bravo AF: 0.697

Asia WGS AF: 0.780 AC: 2711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0050
DANN	Benign	0.64

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: rs2240047; hg19: chr16-19884285;