Genetic Variant GAL:c.-1+561C>T (chr11-68683779-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000933453.1(GAL):c.-1+561C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 152,378 control chromosomes in the GnomAD database, including 34,858 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 0.66 ( 34810 hom., cov: 34)

Exomes 𝑓: 0.77 ( 48 hom. )

Consequence

GAL
ENST00000933453.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.62

Publications

8 publications found

Variant links:

Genes affected

GAL (HGNC:4114): (galanin and GMAP prepropeptide) This gene encodes a neuroendocrine peptide that is widely expressed in the central and peripheral nervous systems and also the gastrointestinal tract, pancreas, adrenal gland and urogenital tract. The encoded protein is a precursor that is proteolytically processed to generate two mature peptides: galanin and galanin message-associated peptide (GMAP). Galanin has diverse physiological functions including nociception, feeding and energy homeostasis, osmotic regulation and water balance. GMAP has been demonstrated to possess antifungal activity and hypothesized to be part of the innate immune system. [provided by RefSeq, Jul 2015]

GAL Gene-Disease associations (from GenCC):

familial temporal lobe epilepsy 8
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

GAL links:

LOC107984343 (HGNC:):

LOC107984343 links:

Genome browser will be placed here

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=-0.98).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000933453.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAL	ENST00000933453.1		c.-1+561C>T		intron	N/A	ENSP00000603512.1
	GAL	ENST00000538401.1	TSL:3	n.1C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.658

AC:

100145

AN:

152098

Hom.:

34797

Cov.:

show subpopulations

Gnomad AFR

AF:

0.422

Gnomad AMI

AF:

0.744

Gnomad AMR

AF:

0.710

Gnomad ASJ

AF:

0.761

Gnomad EAS

AF:

0.869

Gnomad SAS

AF:

0.785

Gnomad FIN

AF:

0.883

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.724

Gnomad OTH

AF:

0.660

GnomAD4 exome

AF:

0.772

AC:

125

AN:

162

Hom.:

Cov.:

AF XY:

0.786

AC XY:

AN XY:

112

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.900

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.800

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.762

AC:

AN:

122

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.658

AC:

100183

AN:

152216

Hom.:

34810

Cov.:

AF XY:

0.670

AC XY:

49833

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.422

AC:

17510

AN:

41518

American (AMR)

AF:

0.710

AC:

10873

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.761

AC:

2641

AN:

3472

East Asian (EAS)

AF:

0.869

AC:

4499

AN:

5176

South Asian (SAS)

AF:

0.785

AC:

3792

AN:

4832

European-Finnish (FIN)

AF:

0.883

AC:

9375

AN:

10616

Middle Eastern (MID)

AF:

0.701

AC:

206

AN:

294

European-Non Finnish (NFE)

AF:

0.724

AC:

49207

AN:

67980

Other (OTH)

AF:

0.664

AC:

1404

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1629

3259

4888

6518

8147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

788

1576

2364

3152

3940

<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:

0.670

Hom.:

4671

Bravo

AF:

0.632

Asia WGS

AF:

0.801

AC:

2788

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

2.7

(source)

DANN

Benign

0.52

PhyloP100

-5.6

Splicing

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