16-19872963-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016235.3(GPRC5B):​c.-1-117G>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
• Publications: 3 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016235.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPRC5B	NM_016235.3	MANE Select	c.-1-117G>A		intron	N/A	NP_057319.1	Q9NZH0-1
	GPRC5B	NM_001304771.1		c.393-117G>A		intron	N/A	NP_001291700.1	B7Z831

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPRC5B	ENST00000300571.7	TSL:1 MANE Select	c.-1-117G>A		intron	N/A	ENSP00000300571.2	Q9NZH0-1
	GPRC5B	ENST00000893194.1		c.-118G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000563253.1
	GPRC5B	ENST00000893194.1		c.-118G>A		5_prime_UTR	Exon 1 of 3	ENSP00000563253.1

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

African (AFR) AF: 0.776 AC: 11614 AN: 14968

American (AMR) AF: 0.504 AC: 12703 AN: 25192

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 11864 AN: 15092

East Asian (EAS) AF: 0.868 AC: 28905 AN: 33300

South Asian (SAS) AF: 0.687 AC: 36260 AN: 52768

European-Finnish (FIN) AF: 0.608 AC: 19793 AN: 32552

Middle Eastern (MID) AF: 0.753 AC: 2092 AN: 2778

European-Non Finnish (NFE) AF: 0.655 AC: 228781 AN: 349402

Other (OTH) AF: 0.682 AC: 20437 AN: 29988

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

African (AFR) AF: 0.778 AC: 32276 AN: 41506

American (AMR) AF: 0.596 AC: 9096 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.798 AC: 2768 AN: 3470

East Asian (EAS) AF: 0.851 AC: 4390 AN: 5158

South Asian (SAS) AF: 0.704 AC: 3390 AN: 4816

European-Finnish (FIN) AF: 0.614 AC: 6485 AN: 10564

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.655 AC: 44545 AN: 67974

Other (OTH) AF: 0.709 AC: 1495 AN: 2108

Alfa AF: 0.668 Hom.: 11665

Bravo AF: 0.697

Asia WGS AF: 0.780 AC: 2711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0050
DANN	Benign	0.64
PhyloP100		-2.0
PromoterAI		-0.0026	Neutral
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: rs2240047; hg19: chr16-19884285;