Variant chr18-77250663-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001480.4(GALR1):c.115G>A(p.Val39Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000823 in 1,458,542 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

GALR1
NM_001480.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.53

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:

LOC124904329 (HGNC:):

LOC124904329 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31678343).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GALR1	NM_001480.4 linkuse as main transcript	c.115G>A	p.Val39Met	missense_variant	1/3	ENST00000299727.5
LOC124904329	XR_007066422.1 linkuse as main transcript	n.604+185C>T		intron_variant, non_coding_transcript_variant
GALR1	XM_017025691.2 linkuse as main transcript	c.115G>A	p.Val39Met	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALR1	ENST00000299727.5 linkuse as main transcript	c.115G>A	p.Val39Met	missense_variant	1/3	1	NM_001480.4	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000205

AC:

AN:

243380

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

132352

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000456

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000823

AC:

AN:

1458542

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

725568

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000990

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2022

The c.115G>A (p.V39M) alteration is located in exon 1 (coding exon 1) of the GALR1 gene. This alteration results from a G to A substitution at nucleotide position 115, causing the valine (V) at amino acid position 39 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Benign

-0.0045

Eigen_PC

Benign

0.079

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.014

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.8

REVEL

Benign

0.096

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.013

Polyphen

0.25

Vest4

0.48

MutPred

0.38

Loss of catalytic residue at V39 (P = 0.0028);

MVP

0.72

MPC

0.70

ClinPred

0.44

GERP RS

3.9

Varity_R

0.15

gMVP

0.41

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over