18-77271099-A-G

Position:

• chr18-77271099-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.*2197A>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 0.067 in 152,184 control chromosomes in the GnomAD database, including 431 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 0.067 (431 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GALR1 NM_001480.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALR1	NM_001480.4	c.*2197A>G		3_prime_UTR_variant	3/3	ENST00000299727.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALR1	ENST00000299727.5	c.*2197A>G		3_prime_UTR_variant	3/3	1	NM_001480.4	P1

Frequencies

GnomAD3 genomes AF: 0.0669 AC: 10173 AN: 152066 Hom.: 422 Cov.: 32

Gnomad AFR AF: 0.0965

Gnomad AMI AF: 0.0562

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.00894

Gnomad EAS AF: 0.0797

Gnomad SAS AF: 0.0334

Gnomad FIN AF: 0.0915

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0422

Gnomad OTH AF: 0.0588

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0670 AC: 10203 AN: 152184 Hom.: 431 Cov.: 32 AF XY: 0.0701 AC XY: 5216 AN XY: 74394

Gnomad4 AFR AF: 0.0968

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.00894

Gnomad4 EAS AF: 0.0797

Gnomad4 SAS AF: 0.0334

Gnomad4 FIN AF: 0.0915

Gnomad4 NFE AF: 0.0422

Gnomad4 OTH AF: 0.0591

Alfa AF: 0.0482 Hom.: 107

Bravo AF: 0.0702

Asia WGS AF: 0.0620 AC: 219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.65

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: rs8097893; hg19: chr18-74983055;