chr18-77250854-G-T

Variant names:

• chr18-77250854-G-T
• rs5375
• NM_001480.4:c.306G>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001480.4(GALR1):​c.306G>T​(p.Val102Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0329 in 1,612,684 control chromosomes in the GnomAD database, including 1,303 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.053 (370 hom., cov: 34)
  • Exomes 𝑓: 0.031 (933 hom.)
• Consequence: GALR1 NM_001480.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 13 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=1.28 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001480.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALR1	NM_001480.4	MANE Select	c.306G>T	p.Val102Val	synonymous	Exon 1 of 3	NP_001471.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALR1	ENST00000299727.5	TSL:1 MANE Select	c.306G>T	p.Val102Val	synonymous	Exon 1 of 3	ENSP00000299727.3
	ENSG00000309801	ENST00000844037.1		n.156C>A		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000309801	ENST00000844038.1		n.65C>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0528 AC: 8043 AN: 152198 Hom.: 369 Cov.: 34

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.0549

Gnomad SAS AF: 0.0373

Gnomad FIN AF: 0.00969

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0272

Gnomad OTH AF: 0.0483

GnomAD2 exomes AF: 0.0358 AC: 8969 AN: 250200 AF XY: 0.0348

Gnomad AFR exome AF: 0.124

Gnomad AMR exome AF: 0.0158

Gnomad ASJ exome AF: 0.0347

Gnomad EAS exome AF: 0.0688

Gnomad FIN exome AF: 0.0115

Gnomad NFE exome AF: 0.0272

Gnomad OTH exome AF: 0.0292

GnomAD4 exome AF: 0.0309 AC: 45063 AN: 1460368 Hom.: 933 Cov.: 36 AF XY: 0.0312 AC XY: 22675 AN XY: 726560

African (AFR) AF: 0.122 AC: 4079 AN: 33478

American (AMR) AF: 0.0162 AC: 723 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0331 AC: 865 AN: 26136

East Asian (EAS) AF: 0.0542 AC: 2150 AN: 39700

South Asian (SAS) AF: 0.0423 AC: 3645 AN: 86258

European-Finnish (FIN) AF: 0.0129 AC: 672 AN: 51940

Middle Eastern (MID) AF: 0.0378 AC: 218 AN: 5768

European-Non Finnish (NFE) AF: 0.0275 AC: 30604 AN: 1111982

Other (OTH) AF: 0.0349 AC: 2107 AN: 60382

GnomAD4 genome AF: 0.0529 AC: 8058 AN: 152316 Hom.: 370 Cov.: 34 AF XY: 0.0504 AC XY: 3756 AN XY: 74482

African (AFR) AF: 0.119 AC: 4965 AN: 41556

American (AMR) AF: 0.0275 AC: 421 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3472

East Asian (EAS) AF: 0.0549 AC: 284 AN: 5176

South Asian (SAS) AF: 0.0373 AC: 180 AN: 4828

European-Finnish (FIN) AF: 0.00969 AC: 103 AN: 10628

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0272 AC: 1853 AN: 68030

Other (OTH) AF: 0.0473 AC: 100 AN: 2112

Alfa AF: 0.0340 Hom.: 234

Bravo AF: 0.0583

Asia WGS AF: 0.0400 AC: 139 AN: 3478

EpiCase AF: 0.0290

EpiControl AF: 0.0280

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	12
DANN	Benign	0.71
PhyloP100		1.3
Mutation Taster		=99/1	polymorphism (auto)

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: rs5375; hg19: chr18-74962810; COSMIC: COSV55317942; COSMIC: COSV55317942;