16-19874418-C-G

Variant names:

• chr16-19874418-C-G
• rs724615
• NM_016235.3:c.-1-1572G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

GPRC5B Gene-Disease associations (from GenCC):

• megalencephalic leukoencephalopathy with subcortical cysts 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• megalencephalic leukoencephalopathy with subcortical cysts 3

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GPRC5B	NM_016235.3	c.-1-1572G>C		intron_variant	Intron 1 of 3	ENST00000300571.7	NP_057319.1
GPRC5B	NM_001304771.1	c.393-1572G>C		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.-1-1572G>C		intron_variant	Intron 1 of 3	1	NM_016235.3	ENSP00000300571.2

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

African (AFR) AF: 0.398 AC: 16501 AN: 41454

American (AMR) AF: 0.297 AC: 4542 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1410 AN: 3470

East Asian (EAS) AF: 0.320 AC: 1652 AN: 5168

South Asian (SAS) AF: 0.157 AC: 757 AN: 4816

European-Finnish (FIN) AF: 0.313 AC: 3311 AN: 10564

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.345 AC: 23486 AN: 67980

Other (OTH) AF: 0.351 AC: 742 AN: 2116

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
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs724615; hg19: chr16-19885740;