6-39072925-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_002062.5(GLP1R):c.573A>G(p.Ala191=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00395 in 1,614,090 control chromosomes in the GnomAD database, including 232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (131 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (101 hom.)
• Consequence: GLP1R NM_002062.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.44

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 6-39072925-A-G is Benign according to our data. Variant chr6-39072925-A-G is described in ClinVar as [Benign]. Clinvar id is 780621.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.44 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLP1R	NM_002062.5	c.573A>G	p.Ala191=	synonymous_variant	6/13	ENST00000373256.5
GLP1R	NR_136562.2	n.633A>G		non_coding_transcript_exon_variant	6/14
GLP1R	NR_136563.2	n.633A>G		non_coding_transcript_exon_variant	6/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLP1R	ENST00000373256.5	c.573A>G	p.Ala191=	synonymous_variant	6/13	1	NM_002062.5	P1

Frequencies

GnomAD3 genomes AF: 0.0214 AC: 3252 AN: 152162 Hom.: 130 Cov.: 33

Gnomad AFR AF: 0.0750

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00556

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00556 AC: 1398 AN: 251426 Hom.: 53 AF XY: 0.00397 AC XY: 539 AN XY: 135884

Gnomad AFR exome AF: 0.0757

Gnomad AMR exome AF: 0.00321

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000325

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00213 AC: 3115 AN: 1461810 Hom.: 101 Cov.: 32 AF XY: 0.00179 AC XY: 1305 AN XY: 727206

Gnomad4 AFR exome AF: 0.0752

Gnomad4 AMR exome AF: 0.00391

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000134

Gnomad4 OTH exome AF: 0.00396

GnomAD4 genome AF: 0.0214 AC: 3255 AN: 152280 Hom.: 131 Cov.: 33 AF XY: 0.0203 AC XY: 1509 AN XY: 74474

Gnomad4 AFR AF: 0.0749

Gnomad4 AMR AF: 0.00556

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.00562 Hom.: 26

Bravo AF: 0.0237

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000237

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

Aug 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	0.47
Dann	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs10305475; hg19: chr6-39040701;