rs539654659

Variant names:

• chr18-77250600-C-A
• rs539654659
• NM_001480.4:c.52C>A

Your query was ambiguous. Multiple possible variants found:

• chr18-77250600-C-A
• chr18-77250600-C-G
• chr18-77250600-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001480.4(GALR1):​c.52C>A​(p.Pro18Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000129 in 1,555,706 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P18S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: GALR1 NM_001480.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047357976).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALR1	NM_001480.4	c.52C>A	p.Pro18Thr	missense_variant	Exon 1 of 3	ENST00000299727.5	NP_001471.2
GALR1	XM_017025691.2	c.52C>A	p.Pro18Thr	missense_variant	Exon 1 of 3		XP_016881180.1
LOC124904329	XR_007066422.1	n.604+248G>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALR1	ENST00000299727.5	c.52C>A	p.Pro18Thr	missense_variant	Exon 1 of 3	1	NM_001480.4	ENSP00000299727.3
ENSG00000309801	ENST00000844037.1	n.162+248G>T		intron_variant	Intron 1 of 1
ENSG00000309801	ENST00000844038.1	n.118+201G>T		intron_variant	Intron 1 of 1
ENSG00000309801	ENST00000844041.1	n.159+248G>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152158 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000125 AC: 2 AN: 159460 AF XY: 0.0000115

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000380

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000843

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1403548 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 694384

African (AFR) AF: 0.00 AC: 0 AN: 32010

American (AMR) AF: 0.0000267 AC: 1 AN: 37414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25256

East Asian (EAS) AF: 0.00 AC: 0 AN: 36474

South Asian (SAS) AF: 0.00 AC: 0 AN: 80914

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5482

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1086964

Other (OTH) AF: 0.00 AC: 0 AN: 58408

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152158 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74328

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.11
DANN	Benign	0.56
DEOGEN2	Benign	0.048	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.11
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.022
Sift	Benign	0.59	T
Sift4G	Benign	0.76	T
Polyphen		0.012	B
Vest4		0.16
MutPred		0.34		Gain of phosphorylation at P18 (P = 0.0148);
MVP		0.23
MPC		0.47
ClinPred		0.023	T
GERP RS		-0.099
Varity_R		0.040
gMVP		0.28

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: rs539654659; hg19: chr18-74962556;