rs6923761

Variant names:

• chr6-39066296-G-A
• rs6923761
• NM_002062.5:c.502G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-39066296-G-A
• chr6-39066296-G-C

Variant summary

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

The NM_002062.5(GLP1R):​c.502G>A​(p.Gly168Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,594,086 control chromosomes in the GnomAD database, including 76,319 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (4890 hom., cov: 33)
  • Exomes 𝑓: 0.30 (71429 hom.)
• Consequence: GLP1R NM_002062.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• Publications: 126 publications found

Genes affected

GLP1R (HGNC:4324): (glucagon like peptide 1 receptor) This gene encodes a 7-transmembrane protein that functions as a receptor for glucagon-like peptide 1 (GLP-1) hormone, which stimulates glucose-induced insulin secretion. This receptor, which functions at the cell surface, becomes internalized in response to GLP-1 and GLP-1 analogs, and it plays an important role in the signaling cascades leading to insulin secretion. It also displays neuroprotective effects in animal models. Polymorphisms in this gene are associated with diabetes. The protein is an important drug target for the treatment of type 2 diabetes and stroke. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0050249994).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLP1R	NM_002062.5	c.502G>A	p.Gly168Ser	missense_variant	Exon 5 of 13	ENST00000373256.5	NP_002053.3
GLP1R	NR_136562.2	n.562G>A		non_coding_transcript_exon_variant	Exon 5 of 14
GLP1R	NR_136563.2	n.562G>A		non_coding_transcript_exon_variant	Exon 5 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLP1R	ENST00000373256.5	c.502G>A	p.Gly168Ser	missense_variant	Exon 5 of 13	1	NM_002062.5	ENSP00000362353.4

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33293 AN: 152040 Hom.: 4888 Cov.: 33

Gnomad AFR AF: 0.0617

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.0116

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.228

GnomAD2 exomes AF: 0.230 AC: 57501 AN: 250114 AF XY: 0.235

Gnomad AFR exome AF: 0.0574

Gnomad AMR exome AF: 0.137

Gnomad ASJ exome AF: 0.238

Gnomad EAS exome AF: 0.0108

Gnomad FIN exome AF: 0.276

Gnomad NFE exome AF: 0.330

Gnomad OTH exome AF: 0.260

GnomAD4 exome AF: 0.300 AC: 432743 AN: 1441928 Hom.: 71429 Cov.: 27 AF XY: 0.297 AC XY: 213090 AN XY: 718444

African (AFR) AF: 0.0522 AC: 1731 AN: 33186

American (AMR) AF: 0.141 AC: 6314 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 6144 AN: 26012

East Asian (EAS) AF: 0.00424 AC: 168 AN: 39638

South Asian (SAS) AF: 0.149 AC: 12815 AN: 85898

European-Finnish (FIN) AF: 0.276 AC: 14651 AN: 53064

Middle Eastern (MID) AF: 0.239 AC: 1377 AN: 5752

European-Non Finnish (NFE) AF: 0.342 AC: 373604 AN: 1093882

Other (OTH) AF: 0.266 AC: 15939 AN: 59856

GnomAD4 genome AF: 0.219 AC: 33287 AN: 152158 Hom.: 4890 Cov.: 33 AF XY: 0.213 AC XY: 15817 AN XY: 74394

African (AFR) AF: 0.0615 AC: 2553 AN: 41524

American (AMR) AF: 0.189 AC: 2885 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 847 AN: 3468

East Asian (EAS) AF: 0.0116 AC: 60 AN: 5156

South Asian (SAS) AF: 0.144 AC: 695 AN: 4822

European-Finnish (FIN) AF: 0.266 AC: 2818 AN: 10596

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22745 AN: 67982

Other (OTH) AF: 0.225 AC: 477 AN: 2116

Alfa AF: 0.285 Hom.: 25527

Bravo AF: 0.204

TwinsUK AF: 0.353 AC: 1310

ALSPAC AF: 0.360 AC: 1386

ESP6500AA AF: 0.0656 AC: 289

ESP6500EA AF: 0.337 AC: 2896

ExAC AF: 0.232 AC: 28145

Asia WGS AF: 0.0700 AC: 246 AN: 3478

EpiCase AF: 0.329

EpiControl AF: 0.319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.84
DEOGEN2	Benign	0.17	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.44	T
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.14	N
PhyloP100		0.11
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.052
Sift	Benign	0.44	T
Sift4G	Benign	0.51	T
Polyphen		0.0010	B
Vest4		0.023
MPC		0.48
ClinPred		0.0010	T
GERP RS		-2.1
Varity_R		0.13
gMVP		0.35
Mutation Taster		=98/2	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: rs6923761; hg19: chr6-39034072; COSMIC: COSV64715250;