rs5376

Positions:

• chr18-77268853-G-A
• chr18-77268853-G-C
• chr18-77268853-G-T

Variant summary

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

The NM_001480.4(GALR1):​c.1001G>A​(p.Ser334Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.984 in 1,613,756 control chromosomes in the GnomAD database, including 784,603 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.91 (64850 hom., cov: 33)
  • Exomes 𝑓: 0.99 (719753 hom.)
• Consequence: GALR1 NM_001480.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480

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 (MetaRNN=1.1790981E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALR1	NM_001480.4	c.1001G>A	p.Ser334Asn	missense_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.1001G>A	p.Ser334Asn	missense_variant	3/3	1	NM_001480.4	ENSP00000299727.3

Frequencies

GnomAD3 genomes AF: 0.914 AC: 139012 AN: 152138 Hom.: 64819 Cov.: 33

Gnomad AFR AF: 0.700

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.967

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.936

GnomAD3 exomes AF: 0.978 AC: 245126 AN: 250604 Hom.: 120553 AF XY: 0.984 AC XY: 133523 AN XY: 135734

Gnomad AFR exome AF: 0.699

Gnomad AMR exome AF: 0.985

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.990

GnomAD4 exome AF: 0.991 AC: 1448899 AN: 1461500 Hom.: 719753 Cov.: 47 AF XY: 0.993 AC XY: 721642 AN XY: 727074

Gnomad4 AFR exome AF: 0.698

Gnomad4 AMR exome AF: 0.983

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.999

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.981

GnomAD4 genome AF: 0.914 AC: 139099 AN: 152256 Hom.: 64850 Cov.: 33 AF XY: 0.918 AC XY: 68318 AN XY: 74454

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.967

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.937

Alfa AF: 0.981 Hom.: 123394

Bravo AF: 0.901

TwinsUK AF: 1.00 AC: 3708

ALSPAC AF: 0.999 AC: 3851

ESP6500AA AF: 0.694 AC: 3058

ESP6500EA AF: 0.999 AC: 8588

ExAC AF: 0.972 AC: 118033

Asia WGS AF: 0.985 AC: 3425 AN: 3478

EpiCase AF: 1.00

EpiControl AF: 0.999

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.15
DANN	Benign	0.36
DEOGEN2	Benign	0.065	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.071	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.84	N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.61	N
REVEL	Benign	0.065
Sift	Benign	0.88	T
Sift4G	Benign	0.68	T
Polyphen		0.0	B
Vest4		0.0060
MPC		0.38
ClinPred		0.00056	T
GERP RS		1.0
Varity_R		0.032
gMVP		0.21

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: rs5376; hg19: chr18-74980809;