rs9959924

Variant names:

• chr18-77255938-T-C
• rs9959924
• NM_001480.4:c.667-220T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GALR1	NM_001480.4	c.667-220T>C		intron_variant	Intron 1 of 2	ENST00000299727.5	NP_001471.2
GALR1	XM_017025691.2	c.667-220T>C		intron_variant	Intron 1 of 2		XP_016881180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALR1	ENST00000299727.5	c.667-220T>C		intron_variant	Intron 1 of 2	1	NM_001480.4	ENSP00000299727.3
GALR1	ENST00000582943.1	n.256-220T>C		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.346 AC: 14351 AN: 41500

American (AMR) AF: 0.170 AC: 2595 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 604 AN: 3468

East Asian (EAS) AF: 0.195 AC: 1009 AN: 5170

South Asian (SAS) AF: 0.121 AC: 584 AN: 4822

European-Finnish (FIN) AF: 0.0442 AC: 470 AN: 10622

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.0813 AC: 5528 AN: 68022

Other (OTH) AF: 0.171 AC: 362 AN: 2114

Alfa AF: 0.117 Hom.: 1786

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
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9959924; hg19: chr18-74967894;