18-77273222-G-T

Variant names:

• chr18-77273222-G-T
• rs2156641
• NM_001480.4:c.*4320G>T

Variant summary

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

The NM_001480.4(GALR1):​c.*4320G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.9 in 152,344 control chromosomes in the GnomAD database, including 62,222 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 0.90 (62117 hom., cov: 30)
  • Exomes 𝑓: 0.96 (105 hom.)
• Consequence: GALR1 NM_001480.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALR1	NM_001480.4	c.*4320G>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000299727.5	NP_001471.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALR1	ENST00000299727.5	c.*4320G>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_001480.4	ENSP00000299727.3

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136716 AN: 152002 Hom.: 62070 Cov.: 30

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.930

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.985

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.901

GnomAD4 exome AF: 0.964 AC: 216 AN: 224 Hom.: 105 Cov.: 0 AF XY: 0.980 AC XY: 147 AN XY: 150

Gnomad4 AFR exome AF: 0.667

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.985

Gnomad4 NFE exome AF: 0.970

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.899 AC: 136825 AN: 152120 Hom.: 62117 Cov.: 30 AF XY: 0.899 AC XY: 66891 AN XY: 74372

Gnomad4 AFR AF: 0.783

Gnomad4 AMR AF: 0.894

Gnomad4 ASJ AF: 0.930

Gnomad4 EAS AF: 0.825

Gnomad4 SAS AF: 0.759

Gnomad4 FIN AF: 0.985

Gnomad4 NFE AF: 0.971

Gnomad4 OTH AF: 0.902

Alfa AF: 0.951 Hom.: 89603

Bravo AF: 0.887

Asia WGS AF: 0.793 AC: 2760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.076
DANN	Benign	0.53

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: rs2156641; hg19: chr18-74985178;