Genetic Variant GALR1:c.732+148T>C (chr18-77256371-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001480.4(GALR1):c.732+148T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 553,294 control chromosomes in the GnomAD database, including 24,798 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 0.30 ( 7166 hom., cov: 31)

Exomes 𝑓: 0.28 ( 17632 hom. )

Consequence

GALR1
NM_001480.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0290

Publications

10 publications found

Variant links:

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]

GALR1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001480.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALR1	NM_001480.4	MANE Select	c.732+148T>C		intron	N/A	NP_001471.2	P47211

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALR1	ENST00000299727.5	TSL:1 MANE Select	c.732+148T>C		intron	N/A	ENSP00000299727.3	P47211
	GALR1	ENST00000582943.1	TSL:3	n.*154T>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.298

AC:

45171

AN:

151744

Hom.:

7142

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.297

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.536

Gnomad SAS

AF:

0.402

Gnomad FIN

AF:

0.244

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.304

GnomAD4 exome

AF:

0.278

AC:

111439

AN:

401432

Hom.:

17632

AF XY:

0.281

AC XY:

60162

AN XY:

214406

show subpopulations

African (AFR)

AF:

0.380

AC:

4239

AN:

11156

American (AMR)

AF:

0.298

AC:

4073

AN:

13652

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

2669

AN:

12416

East Asian (EAS)

AF:

0.551

AC:

15519

AN:

28154

South Asian (SAS)

AF:

0.379

AC:

13452

AN:

35534

European-Finnish (FIN)

AF:

0.235

AC:

6209

AN:

26404

Middle Eastern (MID)

AF:

0.292

AC:

516

AN:

1766

European-Non Finnish (NFE)

AF:

0.235

AC:

58522

AN:

249192

Other (OTH)

AF:

0.269

AC:

6240

AN:

23158

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

3518

7036

10553

14071

17589

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

434

868

1302

1736

2170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.298

AC:

45252

AN:

151862

Hom.:

7166

Cov.:

AF XY:

0.299

AC XY:

22203

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.376

AC:

15570

AN:

41390

American (AMR)

AF:

0.297

AC:

4528

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

714

AN:

3470

East Asian (EAS)

AF:

0.535

AC:

2757

AN:

5156

South Asian (SAS)

AF:

0.403

AC:

1939

AN:

4806

European-Finnish (FIN)

AF:

0.244

AC:

2571

AN:

10538

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.239

AC:

16257

AN:

67932

Other (OTH)

AF:

0.310

AC:

653

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1561

3122

4684

6245

7806

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.266

Hom.:

18433

Bravo

AF:

0.306

Asia WGS

AF:

0.467

AC:

1622

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.0

(source)

DANN

Benign

0.29

PhyloP100

-0.029

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over