3-71754179-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018971.3(GPR27):c.130G>C(p.Val44Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,442,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

GPR27
NM_018971.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55

Publications

0 publications found

Variant links:

Genes affected

GPR27 (HGNC:4482): (G protein-coupled receptor 27) GPR27 is a member of the G protein-coupled receptors (GPCRs), a large family of receptors that have a similar structure characterized by 7 transmembrane domains. Activation of GPCRs by extracellular stimuli such as neurotransmitters, hormones, or light induces an intracellular signaling cascade mediated by heterotrimeric GTP-binding proteins, or G proteins.[supplied by OMIM, May 2010]

GPR27 links:

ENSG00000285708 (HGNC:):

ENSG00000285708 links:

EIF4E3 (HGNC:31837): (eukaryotic translation initiation factor 4E family member 3) EIF4E3 belongs to the EIF4E family of translational initiation factors that interact with the 5-prime cap structure of mRNA and recruit mRNA to the ribosome (Joshi et al., 2004 [PubMed 15153109]).[supplied by OMIM, Mar 2008]

EIF4E3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0341689).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018971.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPR27	NM_018971.3	MANE Select	c.130G>C	p.Val44Leu	missense	Exon 1 of 1	NP_061844.1	F1DAM3
EIF4E3	NM_001134649.3		c.-291+36C>G		intron	N/A	NP_001128121.1	Q8N5X7-2
EIF4E3	NM_173359.5		c.-291+465C>G		intron	N/A	NP_775495.1	Q8N5X7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPR27	ENST00000304411.3	TSL:6 MANE Select	c.130G>C	p.Val44Leu	missense	Exon 1 of 1	ENSP00000303149.2	Q9NS67
ENSG00000285708	ENST00000647725.1		c.-959+36C>G		intron	N/A	ENSP00000497585.1
EIF4E3	ENST00000421769.6	TSL:1	c.-291+465C>G		intron	N/A	ENSP00000411762.2	Q8N5X7-2

Frequencies

GnomAD3 genomes

AF:

0.0000673

AC:

AN:

148688

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000730

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:

0.0000900

Gnomad OTH

AF:

0.000488

GnomAD2 exomes

AF:

0.000116

AC:

AN:

172996

AF XY:

0.0000812

show subpopulations

Gnomad AFR exome

AF:

0.000117

Gnomad AMR exome

AF:

0.000350

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000112

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000166

AC:

215

AN:

1293944

Hom.:

Cov.:

AF XY:

0.000158

AC XY:

102

AN XY:

645154

show subpopulations

African (AFR)

AF:

0.0000381

AC:

AN:

26258

American (AMR)

AF:

0.000294

AC:

AN:

34002

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20794

East Asian (EAS)

AF:

0.00

AC:

AN:

27534

South Asian (SAS)

AF:

0.0000261

AC:

AN:

76652

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34146

Middle Eastern (MID)

AF:

0.000241

AC:

AN:

4150

European-Non Finnish (NFE)

AF:

0.000189

AC:

193

AN:

1019998

Other (OTH)

AF:

0.000159

AC:

AN:

50410

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000673

AC:

AN:

148688

Hom.:

Cov.:

AF XY:

0.0000552

AC XY:

AN XY:

72502

show subpopulations

African (AFR)

AF:

0.0000730

AC:

AN:

41112

American (AMR)

AF:

0.00

AC:

AN:

14966

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3400

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9274

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000900

AC:

AN:

66678

Other (OTH)

AF:

0.000488

AC:

AN:

2048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000681

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.012

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.45

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.034

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.6

PhyloP100

1.5

PrimateAI

Uncertain

0.72

PROVEAN

Benign

0.44

REVEL

Benign

0.029

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.094

MutPred

0.57

Gain of helix (P = 0.0854)

MVP

0.068

ClinPred

0.015

GERP RS

0.31

PromoterAI

-0.0050

Neutral

(source)

Varity_R

0.089

gMVP

0.057

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over