16-19872407-C-T

Position:

• chr16-19872407-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_016235.3(GPRC5B):​c.439G>A​(p.Val147Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,613,534 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0059 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00064 (12 hom.)
• Consequence: GPRC5B NM_016235.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.54

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009661317).
• BP6: Variant 16-19872407-C-T is Benign according to our data. Variant chr16-19872407-C-T is described in ClinVar as [Benign]. Clinvar id is 718205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00589 (897/152312) while in subpopulation AFR AF= 0.0204 (849/41574). AF 95% confidence interval is 0.0193. There are 6 homozygotes in gnomad4. There are 419 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 897 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPRC5B	NM_016235.3	c.439G>A	p.Val147Met	missense_variant	2/4	ENST00000300571.7	NP_057319.1
GPRC5B	NM_001304771.1	c.832G>A	p.Val278Met	missense_variant	2/4		NP_001291700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPRC5B	ENST00000300571.7	c.439G>A	p.Val147Met	missense_variant	2/4	1	NM_016235.3	ENSP00000300571.2

Frequencies

GnomAD3 genomes AF: 0.00589 AC: 897 AN: 152194 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00168 AC: 417 AN: 248920 Hom.: 10 AF XY: 0.00130 AC XY: 176 AN XY: 135072

Gnomad AFR exome AF: 0.0215

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000188

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.000639 AC: 934 AN: 1461222 Hom.: 12 Cov.: 34 AF XY: 0.000578 AC XY: 420 AN XY: 726894

Gnomad4 AFR exome AF: 0.0207

Gnomad4 AMR exome AF: 0.00137

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.0000684

Gnomad4 OTH exome AF: 0.00156

GnomAD4 genome AF: 0.00589 AC: 897 AN: 152312 Hom.: 6 Cov.: 32 AF XY: 0.00563 AC XY: 419 AN XY: 74474

Gnomad4 AFR AF: 0.0204

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00117 Hom.: 7

Bravo AF: 0.00680

ESP6500AA AF: 0.0205 AC: 90

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00202 AC: 245

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T;.;T;T;.;.
Eigen	Benign	0.18
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.91	.;D;.;D;D;D
MetaRNN	Benign	0.0097	T;T;T;T;T;T
MetaSVM	Uncertain	0.10	D
MutationAssessor	Benign	1.8	L;L;L;L;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.55	N;N;N;N;N;N
REVEL	Uncertain	0.43
Sift	Uncertain	0.0050	D;D;D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D;.;.
Polyphen		0.99	D;.;D;D;.;.
Vest4		0.48
MVP		0.62
MPC		1.1
ClinPred		0.014	T
GERP RS		3.3
Varity_R		0.061
gMVP		0.50

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: rs114262543; hg19: chr16-19883729;