6-39065724-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002062.5(GLP1R):c.297C>T(p.His99=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000379 in 1,565,606 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00020 (1 hom.)
• Consequence: GLP1R NM_002062.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.73

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

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 6-39065724-C-T is Benign according to our data. Variant chr6-39065724-C-T is described in ClinVar as [Benign]. Clinvar id is 768087.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.72 with no splicing effect.
• BS2: High AC in GnomAd at 300 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLP1R	NM_002062.5	c.297C>T	p.His99=	synonymous_variant	4/13	ENST00000373256.5
GLP1R	NR_136562.2	n.357C>T		non_coding_transcript_exon_variant	4/14
GLP1R	NR_136563.2	n.357C>T		non_coding_transcript_exon_variant	4/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLP1R	ENST00000373256.5	c.297C>T	p.His99=	synonymous_variant	4/13	1	NM_002062.5	P1

Frequencies

GnomAD3 genomes AF: 0.00197 AC: 300 AN: 152194 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00699

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000500 AC: 88 AN: 176100 Hom.: 0 AF XY: 0.000364 AC XY: 34 AN XY: 93396

Gnomad AFR exome AF: 0.00682

Gnomad AMR exome AF: 0.000300

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000778

Gnomad SAS exome AF: 0.0000417

Gnomad FIN exome AF: 0.0000615

Gnomad NFE exome AF: 0.0000829

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000204 AC: 289 AN: 1413294 Hom.: 1 Cov.: 31 AF XY: 0.000176 AC XY: 123 AN XY: 698420

Gnomad4 AFR exome AF: 0.00589

Gnomad4 AMR exome AF: 0.000320

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000271

Gnomad4 SAS exome AF: 0.0000373

Gnomad4 FIN exome AF: 0.0000993

Gnomad4 NFE exome AF: 0.0000488

Gnomad4 OTH exome AF: 0.000393

GnomAD4 genome AF: 0.00200 AC: 305 AN: 152312 Hom.: 1 Cov.: 33 AF XY: 0.00197 AC XY: 147 AN XY: 74466

Gnomad4 AFR AF: 0.00707

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00108 Hom.: 0

Bravo AF: 0.00206

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 04, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	0.32
Dann	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs144122530; hg19: chr6-39033500;