NM_001480.4:c.448C>G

Variant names:

• chr18-77250996-C-G
• rs141065471
• NM_001480.4:c.448C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001480.4(GALR1):​c.448C>G​(p.Arg150Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,604,640 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: GALR1 NM_001480.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.70
• Publications: 5 publications found

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]

ENSG00000309801 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALR1	NM_001480.4	c.448C>G	p.Arg150Gly	missense_variant	Exon 1 of 3	ENST00000299727.5	NP_001471.2
GALR1	XM_017025691.2	c.448C>G	p.Arg150Gly	missense_variant	Exon 1 of 3		XP_016881180.1
LOC124904329	XR_007066422.1	n.456G>C		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALR1	ENST00000299727.5	c.448C>G	p.Arg150Gly	missense_variant	Exon 1 of 3	1	NM_001480.4	ENSP00000299727.3
ENSG00000309801	ENST00000844037.1	n.14G>C		non_coding_transcript_exon_variant	Exon 1 of 2
ENSG00000309801	ENST00000844041.1	n.11G>C		non_coding_transcript_exon_variant	Exon 1 of 2
ENSG00000309801	ENST00000844038.1	n.-78G>C		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 152220 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

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: 0.000250

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000135 AC: 33 AN: 243730 AF XY: 0.000151

Gnomad AFR exome AF: 0.000187

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000249

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000121 AC: 176 AN: 1452302 Hom.: 0 Cov.: 36 AF XY: 0.000105 AC XY: 76 AN XY: 722926

African (AFR) AF: 0.0000597 AC: 2 AN: 33474

American (AMR) AF: 0.0000224 AC: 1 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86240

European-Finnish (FIN) AF: 0.0000453 AC: 2 AN: 44128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000147 AC: 164 AN: 1111870

Other (OTH) AF: 0.0000995 AC: 6 AN: 60326

GnomAD4 genome AF: 0.000236 AC: 36 AN: 152338 Hom.: 0 Cov.: 33 AF XY: 0.000322 AC XY: 24 AN XY: 74490

African (AFR) AF: 0.000337 AC: 14 AN: 41582

American (AMR) AF: 0.000327 AC: 5 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000848 Hom.: 0

Bravo AF: 0.000253

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000223 AC: 27

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.448C>G (p.R150G) alteration is located in exon 1 (coding exon 1) of the GALR1 gene. This alteration results from a C to G substitution at nucleotide position 448, causing the arginine (R) at amino acid position 150 to be replaced by a glycine (G). 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	0.20
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Benign	0.044
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.7
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.21
Sift	Benign	0.045	D
Sift4G	Uncertain	0.051	T
Polyphen		0.076	B
Vest4		0.73
MVP		0.67
MPC		0.83
ClinPred		0.088	T
GERP RS		4.5
Varity_R		0.83
gMVP		0.71
Mutation Taster		=21/79	disease causing

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

Other links and lift over

dbSNP: rs141065471; hg19: chr18-74962952;