X-130384742-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_178471.3(GPR119):c.706C>G(p.Leu236Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 1,210,292 control chromosomes in the GnomAD database, including 7 homozygotes. There are 1,303 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., 73 hem., cov: 23)
  • Exomes 𝑓: 0.0032 (6 hom. 1230 hem.)
• Consequence: GPR119 NM_178471.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.35

Genes affected

GPR119 (HGNC:19060): (G protein-coupled receptor 119) This gene encodes a member of the rhodopsin subfamily of G-protein-coupled receptors that is expressed in the pancreas and gastrointestinal tract. The encoded protein is activated by lipid amides including lysophosphatidylcholine and oleoylethanolamide and may be involved in glucose homeostasis. This protein is a potential drug target in the treatment of type 2 diabetes.[provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012250364).
• BP6: Variant X-130384742-G-C is Benign according to our data. Variant chrX-130384742-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 778985.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-130384742-G-C is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00324 (3563/1098114) while in subpopulation MID AF= 0.0196 (81/4134). AF 95% confidence interval is 0.0162. There are 6 homozygotes in gnomad4_exome. There are 1230 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 73 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR119	NM_178471.3	c.706C>G	p.Leu236Val	missense_variant	1/2	ENST00000682440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR119	ENST00000682440.1	c.706C>G	p.Leu236Val	missense_variant	1/2		NM_178471.3	P1
GPR119	ENST00000276218.4	c.706C>G	p.Leu236Val	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes AF: 0.00229 AC: 257 AN: 112124 Hom.: 1 Cov.: 23 AF XY: 0.00213 AC XY: 73 AN XY: 34268

Gnomad AFR AF: 0.000648

Gnomad AMI AF: 0.00733

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.000755

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00297

Gnomad FIN AF: 0.000821

Gnomad MID AF: 0.00833

Gnomad NFE AF: 0.00363

Gnomad OTH AF: 0.00399

GnomAD3 exomes AF: 0.00219 AC: 402 AN: 183268 Hom.: 0 AF XY: 0.00245 AC XY: 166 AN XY: 67760

Gnomad AFR exome AF: 0.000456

Gnomad AMR exome AF: 0.000839

Gnomad ASJ exome AF: 0.00147

Gnomad EAS exome AF: 0.0000722

Gnomad SAS exome AF: 0.00246

Gnomad FIN exome AF: 0.000875

Gnomad NFE exome AF: 0.00350

Gnomad OTH exome AF: 0.00309

GnomAD4 exome AF: 0.00324 AC: 3563 AN: 1098114 Hom.: 6 Cov.: 32 AF XY: 0.00338 AC XY: 1230 AN XY: 363468

Gnomad4 AFR exome AF: 0.000568

Gnomad4 AMR exome AF: 0.000795

Gnomad4 ASJ exome AF: 0.000671

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00325

Gnomad4 FIN exome AF: 0.00148

Gnomad4 NFE exome AF: 0.00360

Gnomad4 OTH exome AF: 0.00338

GnomAD4 genome AF: 0.00228 AC: 256 AN: 112178 Hom.: 1 Cov.: 23 AF XY: 0.00213 AC XY: 73 AN XY: 34332

Gnomad4 AFR AF: 0.000647

Gnomad4 AMR AF: 0.00151

Gnomad4 ASJ AF: 0.000755

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00297

Gnomad4 FIN AF: 0.000821

Gnomad4 NFE AF: 0.00363

Gnomad4 OTH AF: 0.00394

Alfa AF: 0.00287 Hom.: 20

Bravo AF: 0.00207

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00208 AC: 6

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.00386 AC: 26

ExAC AF: 0.00245 AC: 297

EpiCase AF: 0.00523

EpiControl AF: 0.00486

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	19
Dann	Uncertain	0.99
DEOGEN2	Benign	0.025	T
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.68	T
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	0.71	D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.10
Sift	Benign	0.40	T
Sift4G	Benign	0.43	T
Polyphen		0.91	P
Vest4		0.052
MVP		0.72
MPC		0.98
ClinPred		0.018	T
GERP RS		4.3
Varity_R		0.17
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs41310452; hg19: chrX-129518716; COSMIC: COSV105008926;