rs2717162

Positions:

• chr18-77256371-T-C
• chr18-77256371-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001480.4(GALR1):​c.732+148T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 553,294 control chromosomes in the GnomAD database, including 24,798 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 0.30 (7166 hom., cov: 31)
  • Exomes 𝑓: 0.28 (17632 hom.)
• Consequence: GALR1 NM_001480.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALR1	NM_001480.4	c.732+148T>C		intron_variant		ENST00000299727.5
GALR1	XM_017025691.2	c.732+148T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALR1	ENST00000299727.5	c.732+148T>C		intron_variant		1	NM_001480.4	P1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45171 AN: 151744 Hom.: 7142 Cov.: 31

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.304

GnomAD4 exome AF: 0.278 AC: 111439 AN: 401432 Hom.: 17632 AF XY: 0.281 AC XY: 60162 AN XY: 214406

Gnomad4 AFR exome AF: 0.380

Gnomad4 AMR exome AF: 0.298

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.551

Gnomad4 SAS exome AF: 0.379

Gnomad4 FIN exome AF: 0.235

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.269

GnomAD4 genome AF: 0.298 AC: 45252 AN: 151862 Hom.: 7166 Cov.: 31 AF XY: 0.299 AC XY: 22203 AN XY: 74222

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.535

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.310

Alfa AF: 0.256 Hom.: 7102

Bravo AF: 0.306

Asia WGS AF: 0.467 AC: 1622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.0
DANN	Benign	0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs2717162; hg19: chr18-74968327;