rs9959924

Positions:

• chr18-77255938-T-C

Variant summary

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

The NM_001480.4(GALR1):​c.667-220T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,218 control chromosomes in the GnomAD database, including 3,283 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 0.17 (3283 hom., cov: 32)
• Consequence: GALR1 NM_001480.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.923

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALR1	NM_001480.4	c.667-220T>C		intron_variant		ENST00000299727.5
GALR1	XM_017025691.2	c.667-220T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALR1	ENST00000299727.5	c.667-220T>C		intron_variant		1	NM_001480.4	P1
GALR1	ENST00000582943.1	n.256-220T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25569 AN: 152100 Hom.: 3274 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0442

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0813

Gnomad OTH AF: 0.172

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.168 AC: 25617 AN: 152218 Hom.: 3283 Cov.: 32 AF XY: 0.165 AC XY: 12280 AN XY: 74444

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.0442

Gnomad4 NFE AF: 0.0813

Gnomad4 OTH AF: 0.171

Alfa AF: 0.106 Hom.: 1031

Bravo AF: 0.189

Asia WGS AF: 0.179 AC: 622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.65
DANN	Benign	0.75

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: rs9959924; hg19: chr18-74967894;