11-94380767-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_016540.4(GPR83):c.654C>A(p.Asp218Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000764 in 1,607,738 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00049 (8 hom.)
• Consequence: GPR83 NM_016540.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.337

Genes affected

GPR83 (HGNC:4523): (G protein-coupled receptor 83) Predicted to enable neuropeptide receptor activity. Predicted to be involved in neuropeptide signaling pathway. Predicted to act upstream of or within response to glucocorticoid. Located in cilium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028385222).
• BP6: Variant 11-94380767-G-T is Benign according to our data. Variant chr11-94380767-G-T is described in ClinVar as [Benign]. Clinvar id is 782544.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR83	NM_016540.4	c.654C>A	p.Asp218Glu	missense_variant	4/4	ENST00000243673.7
GPR83	NM_001330345.2	c.528C>A	p.Asp176Glu	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR83	ENST00000243673.7	c.654C>A	p.Asp218Glu	missense_variant	4/4	1	NM_016540.4	P1
GPR83	ENST00000539203.2	c.528C>A	p.Asp176Glu	missense_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.00336 AC: 510 AN: 151920 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00384

GnomAD3 exomes AF: 0.00129 AC: 319 AN: 247694 Hom.: 3 AF XY: 0.00105 AC XY: 140 AN XY: 133710

Gnomad AFR exome AF: 0.0111

Gnomad AMR exome AF: 0.00131

Gnomad ASJ exome AF: 0.00711

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000662

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000152

Gnomad OTH exome AF: 0.000825

GnomAD4 exome AF: 0.000493 AC: 717 AN: 1455700 Hom.: 8 Cov.: 33 AF XY: 0.000474 AC XY: 343 AN XY: 723548

Gnomad4 AFR exome AF: 0.0108

Gnomad4 AMR exome AF: 0.00126

Gnomad4 ASJ exome AF: 0.00574

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000582

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000604

Gnomad4 OTH exome AF: 0.00120

GnomAD4 genome AF: 0.00337 AC: 512 AN: 152038 Hom.: 4 Cov.: 32 AF XY: 0.00335 AC XY: 249 AN XY: 74296

Gnomad4 AFR AF: 0.0105

Gnomad4 AMR AF: 0.00210

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00380

Alfa AF: 0.000770 Hom.: 2

Bravo AF: 0.00381

ESP6500AA AF: 0.0109 AC: 48

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00128 AC: 155

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000178

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

Apr 17, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	6.7
Dann	Benign	0.44
DEOGEN2	Benign	0.049	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.73	T;T
MetaRNN	Benign	0.0028	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.92	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.080	N;N
REVEL	Benign	0.15
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.046
MutPred		0.32		Gain of methylation at K214 (P = 0.1039);.;
MVP		0.28
MPC		0.044
ClinPred		0.0011	T
GERP RS		-2.1
Varity_R		0.026
gMVP		0.34

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: rs61734489; hg19: chr11-94113933;