16-19861207-T-G

Variant names:

• chr16-19861207-T-G
• rs876856
• NM_016235.3:c.1167+630A>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.1167+630A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 151,866 control chromosomes in the GnomAD database, including 1,228 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 0.11 (1228 hom., cov: 32)
• Consequence: GPRC5B NM_016235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.871
• Publications: 2 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=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 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.1167+630A>C		intron	N/A	NP_057319.1	Q9NZH0-1
	GPRC5B	NM_001304771.1		c.1560+630A>C		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.1167+630A>C		intron	N/A	ENSP00000300571.2	Q9NZH0-1
	GPRC5B	ENST00000535671.5	TSL:1	c.1167+630A>C		intron	N/A	ENSP00000442858.1	Q9NZH0-2
	GPRC5B	ENST00000562348.1	TSL:1	n.504+630A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16962 AN: 151754 Hom.: 1228 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.0354

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0678

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.112 AC: 16991 AN: 151866 Hom.: 1228 Cov.: 32 AF XY: 0.114 AC XY: 8429 AN XY: 74206

African (AFR) AF: 0.153 AC: 6315 AN: 41408

American (AMR) AF: 0.175 AC: 2671 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 438 AN: 3468

East Asian (EAS) AF: 0.254 AC: 1312 AN: 5162

South Asian (SAS) AF: 0.211 AC: 1014 AN: 4804

European-Finnish (FIN) AF: 0.0354 AC: 373 AN: 10542

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.0678 AC: 4606 AN: 67946

Other (OTH) AF: 0.113 AC: 237 AN: 2106

Alfa AF: 0.0520 Hom.: 50

Bravo AF: 0.125

Asia WGS AF: 0.247 AC: 856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.6
DANN	Benign	0.81
PhyloP100		-0.87
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs876856; hg19: chr16-19872529;