chr18-77250556-T-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001480.4(GALR1):c.8T>G(p.Leu3Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000327 in 1,529,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

GALR1
NM_001480.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.956

Publications

0 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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37641802).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALR1	NM_001480.4 link	c.8T>G	p.Leu3Arg	missense_variant	Exon 1 of 3	ENST00000299727.5	NP_001471.2	P47211
GALR1	XM_017025691.2 link	c.8T>G	p.Leu3Arg	missense_variant	Exon 1 of 3		XP_016881180.1
LOC124904329	XR_007066422.1 link	n.604+292A>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GALR1	ENST00000299727.5 link	c.8T>G	p.Leu3Arg	missense_variant	Exon 1 of 3	1	NM_001480.4	ENSP00000299727.3	P47211
ENSG00000309801	ENST00000844037.1 link	n.162+292A>C		intron_variant	Intron 1 of 1
ENSG00000309801	ENST00000844038.1 link	n.118+245A>C		intron_variant	Intron 1 of 1
ENSG00000309801	ENST00000844041.1 link	n.159+292A>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000775

AC:

AN:

128990

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000203

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000290

AC:

AN:

1377042

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

678756

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31416

American (AMR)

AF:

0.00

AC:

AN:

35482

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24458

East Asian (EAS)

AF:

0.00

AC:

AN:

35684

South Asian (SAS)

AF:

0.00

AC:

AN:

77964

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4648

European-Non Finnish (NFE)

AF:

0.00000372

AC:

AN:

1075400

Other (OTH)

AF:

0.00

AC:

AN:

57502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152056

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41420

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5126

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:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67988

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 10, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.8T>G (p.L3R) alteration is located in exon 1 (coding exon 1) of the GALR1 gene. This alteration results from a T to G substitution at nucleotide position 8, causing the leucine (L) at amino acid position 3 to be replaced by an arginine (R). 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

0.14

BayesDel_addAF

Benign

-0.027

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.068

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.47

M_CAP

Benign

0.042

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.1

PhyloP100

0.96

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.81

REVEL

Benign

0.10

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0070

Polyphen

0.18

Vest4

0.70

MutPred

0.36

Loss of stability (P = 0.0359);

MVP

0.66

MPC

0.80

ClinPred

0.35

GERP RS

2.1

Varity_R

0.28

gMVP

0.73

Mutation Taster

=91/9

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over