17-81809046-C-T

Position:

• chr17-81809046-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_000160.5(GCGR):​c.28C>T​(p.Leu10Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000586 in 1,536,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: GCGR NM_000160.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.877

Genes affected

GCGR (HGNC:4192): (glucagon receptor) The protein encoded by this gene is a glucagon receptor that is important in controlling blood glucose levels. Defects in this gene are a cause of non-insulin-dependent diabetes mellitus (NIDDM).[provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 17-81809046-C-T is Benign according to our data. Variant chr17-81809046-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3608845.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.877 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCGR	NM_000160.5	c.28C>T	p.Leu10Leu	synonymous_variant	2/14	ENST00000400723.8	NP_000151.1
GCGR	XM_006722277.2	c.28C>T	p.Leu10Leu	synonymous_variant	2/14		XP_006722340.1
GCGR	XM_017024446.2	c.28C>T	p.Leu10Leu	synonymous_variant	2/14		XP_016879935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCGR	ENST00000400723.8	c.28C>T	p.Leu10Leu	synonymous_variant	2/14	1	NM_000160.5	ENSP00000383558.3
GCGR	ENST00000572185.1	n.323C>T		non_coding_transcript_exon_variant	2/3	1
GCGR	ENST00000570996.5	c.28C>T	p.Leu10Leu	synonymous_variant	2/12	2		ENSP00000460976.1
GCGR	ENST00000573428.1	c.28C>T	p.Leu10Leu	synonymous_variant	2/4	4		ENSP00000458930.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152262 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000361 AC: 5 AN: 1383810 Hom.: 0 Cov.: 32 AF XY: 0.00000293 AC XY: 2 AN XY: 682828

Gnomad4 AFR exome AF: 0.0000950

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000345

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152262 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74384

Gnomad4 AFR AF: 0.0000723

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.4
DANN	Benign	0.84

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: rs961902777; hg19: chr17-79766922;