rs2717128

Positions:

• chr18-77275676-A-G

Variant summary

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

The NM_001480.4(GALR1):​c.*6774A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,172 control chromosomes in the GnomAD database, including 1,532 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 0.14 (1532 hom., cov: 33)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: GALR1 NM_001480.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALR1	NM_001480.4	c.*6774A>G		3_prime_UTR_variant	3/3	ENST00000299727.5	NP_001471.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALR1	ENST00000299727.5	c.*6774A>G		3_prime_UTR_variant	3/3	1	NM_001480.4	ENSP00000299727.3

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21001 AN: 152050 Hom.: 1522 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0611

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.0803

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 EAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.138 AC: 21034 AN: 152168 Hom.: 1532 Cov.: 33 AF XY: 0.137 AC XY: 10179 AN XY: 74380

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.0611

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.0803

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.124

Alfa AF: 0.132 Hom.: 2826

Bravo AF: 0.143

Asia WGS AF: 0.120 AC: 420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.46

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: rs2717128; hg19: chr18-74987632;