18-77250600-C-T

Variant names:

Variant summary

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

The NM_001480.4(GALR1):c.52C>T(p.Pro18Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000816 in 1,555,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

GALR1
NM_001480.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: -0.106

Publications

1 publications found

Variant links:

Genes affected

GALR1 (HGNC:4132): (galanin receptor 1) The neuropeptide galanin elicits a range of biological effects by interaction with specific G-protein-coupled receptors. Galanin receptors are seven-transmembrane proteins shown to activate a variety of intracellular second-messenger pathways. GALR1 inhibits adenylyl cyclase via a G protein of the Gi/Go family. GALR1 is widely expressed in the brain and spinal cord, as well as in peripheral sites such as the small intestine and heart. [provided by RefSeq, Jul 2008]

GALR1 links:

ENSG00000309801 (HGNC:):

ENSG00000309801 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=0.004375577).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALR1	NM_001480.4 link	c.52C>T	p.Pro18Ser	missense_variant	Exon 1 of 3	ENST00000299727.5	NP_001471.2	P47211
GALR1	XM_017025691.2 link	c.52C>T	p.Pro18Ser	missense_variant	Exon 1 of 3		XP_016881180.1
LOC124904329	XR_007066422.1 link	n.604+248G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GALR1	ENST00000299727.5 link	c.52C>T	p.Pro18Ser	missense_variant	Exon 1 of 3	1	NM_001480.4	ENSP00000299727.3	P47211
ENSG00000309801	ENST00000844037.1 link	n.162+248G>A		intron_variant	Intron 1 of 1
ENSG00000309801	ENST00000844038.1 link	n.118+201G>A		intron_variant	Intron 1 of 1
ENSG00000309801	ENST00000844041.1 link	n.159+248G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.000486

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000119

AC:

AN:

159460

AF XY:

0.0000802

show subpopulations

Gnomad AFR exome

AF:

0.00189

Gnomad AMR exome

AF:

0.000114

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000152

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000378

AC:

AN:

1403548

Hom.:

Cov.:

AF XY:

0.0000317

AC XY:

AN XY:

694384

show subpopulations

African (AFR)

AF:

0.00122

AC:

AN:

32010

American (AMR)

AF:

0.000160

AC:

AN:

37414

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25256

East Asian (EAS)

AF:

0.00

AC:

AN:

36474

South Asian (SAS)

AF:

0.00

AC:

AN:

80914

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5482

European-Non Finnish (NFE)

AF:

0.00000184

AC:

AN:

1086964

Other (OTH)

AF:

0.000103

AC:

AN:

58408

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000486

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00171

AC:

AN:

41566

American (AMR)

AF:

0.000196

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000612

ExAC

AF:

0.0000861

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 20, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.52C>T (p.P18S) alteration is located in exon 1 (coding exon 1) of the GALR1 gene. This alteration results from a C to T substitution at nucleotide position 52, causing the proline (P) at amino acid position 18 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

GALR1-related disorder

Benign:1

Nov 08, 2022

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.088

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.045

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.35

M_CAP

Benign

0.0046

MetaRNN

Benign

0.0044

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.51

PhyloP100

-0.11

PrimateAI

Benign

0.40

PROVEAN

Benign

0.16

REVEL

Benign

0.025

Sift

Benign

0.74

Sift4G

Benign

0.95

Polyphen

0.0

Vest4

0.086

MutPred

0.38

Loss of catalytic residue at P18 (P = 1e-04);

MVP

0.21

MPC

0.42

ClinPred

0.0072

GERP RS

-0.099

Varity_R

0.029

gMVP

0.29

Mutation Taster

=92/8

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.

18-77250600-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over