rs5374

Positions:

• chr18-77250689-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001480.4(GALR1):​c.141T>C​(p.Gly47=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 1,612,500 control chromosomes in the GnomAD database, including 308,168 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 0.57 (25560 hom., cov: 33)
  • Exomes 𝑓: 0.62 (282608 hom.)
• Consequence: GALR1 NM_001480.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280

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]

LOC124904329 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=-0.28 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALR1	NM_001480.4	c.141T>C	p.Gly47=	synonymous_variant	1/3	ENST00000299727.5
LOC124904329	XR_007066422.1	n.604+159A>G		intron_variant, non_coding_transcript_variant
GALR1	XM_017025691.2	c.141T>C	p.Gly47=	synonymous_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALR1	ENST00000299727.5	c.141T>C	p.Gly47=	synonymous_variant	1/3	1	NM_001480.4	P1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86675 AN: 151944 Hom.: 25555 Cov.: 33

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.586

GnomAD3 exomes AF: 0.570 AC: 141504 AN: 248438 Hom.: 42022 AF XY: 0.582 AC XY: 78365 AN XY: 134720

Gnomad AFR exome AF: 0.481

Gnomad AMR exome AF: 0.375

Gnomad ASJ exome AF: 0.761

Gnomad EAS exome AF: 0.370

Gnomad SAS exome AF: 0.561

Gnomad FIN exome AF: 0.618

Gnomad NFE exome AF: 0.649

Gnomad OTH exome AF: 0.593

GnomAD4 exome AF: 0.617 AC: 900605 AN: 1460438 Hom.: 282608 Cov.: 70 AF XY: 0.618 AC XY: 448799 AN XY: 726572

Gnomad4 AFR exome AF: 0.480

Gnomad4 AMR exome AF: 0.385

Gnomad4 ASJ exome AF: 0.758

Gnomad4 EAS exome AF: 0.320

Gnomad4 SAS exome AF: 0.562

Gnomad4 FIN exome AF: 0.624

Gnomad4 NFE exome AF: 0.641

Gnomad4 OTH exome AF: 0.619

GnomAD4 genome AF: 0.570 AC: 86713 AN: 152062 Hom.: 25560 Cov.: 33 AF XY: 0.569 AC XY: 42324 AN XY: 74332

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.773

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.580

Alfa AF: 0.634 Hom.: 64572

Bravo AF: 0.553

Asia WGS AF: 0.423 AC: 1470 AN: 3476

EpiCase AF: 0.658

EpiControl AF: 0.662

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.70

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

LitVar

Other links and lift over

dbSNP: rs5374; hg19: chr18-74962645; COSMIC: COSV55316040; COSMIC: COSV55316040;