11-68684970-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_015973.5(GAL):c.47C>T(p.Ala16Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00922 in 1,608,498 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0078 ( 13 hom., cov: 33)

Exomes 𝑓: 0.0094 ( 99 hom. )

Consequence

GAL
NM_015973.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0120

Publications

5 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037229955).

BP6

Variant 11-68684970-C-T is Benign according to our data. Variant chr11-68684970-C-T is described in ClinVar as Benign. ClinVar VariationId is 475915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1187 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015973.5. 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
	GAL	NM_015973.5	MANE Select	c.47C>T	p.Ala16Val	missense	Exon 2 of 6	NP_057057.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GAL	ENST00000265643.4	TSL:1 MANE Select	c.47C>T	p.Ala16Val	missense	Exon 2 of 6	ENSP00000265643.3	P22466
GAL	ENST00000933457.1		c.47C>T	p.Ala16Val	missense	Exon 2 of 7	ENSP00000603516.1
GAL	ENST00000933456.1		c.47C>T	p.Ala16Val	missense	Exon 2 of 6	ENSP00000603515.1

Frequencies

GnomAD3 genomes

AF:

0.00780

AC:

1188

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.00549

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00696

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0117

Gnomad OTH

AF:

0.00812

GnomAD2 exomes

AF:

0.00681

AC:

1586

AN:

232814

AF XY:

0.00667

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.00354

Gnomad ASJ exome

AF:

0.0174

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00821

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.00821

GnomAD4 exome

AF:

0.00937

AC:

13650

AN:

1456160

Hom.:

Cov.:

AF XY:

0.00925

AC XY:

6697

AN XY:

724198

show subpopulations

African (AFR)

AF:

0.00177

AC:

AN:

33354

American (AMR)

AF:

0.00383

AC:

170

AN:

44442

Ashkenazi Jewish (ASJ)

AF:

0.0178

AC:

462

AN:

25954

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39580

South Asian (SAS)

AF:

0.000820

AC:

AN:

85348

European-Finnish (FIN)

AF:

0.00901

AC:

469

AN:

52030

Middle Eastern (MID)

AF:

0.0158

AC:

AN:

5648

European-Non Finnish (NFE)

AF:

0.0107

AC:

11824

AN:

1109728

Other (OTH)

AF:

0.00841

AC:

505

AN:

60076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

602

1204

1805

2407

3009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

424

848

1272

1696

2120

<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:

0.00779

AC:

1187

AN:

152338

Hom.:

Cov.:

AF XY:

0.00714

AC XY:

532

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.00216

AC:

AN:

41580

American (AMR)

AF:

0.00549

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.0161

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00145

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00696

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0117

AC:

796

AN:

68014

Other (OTH)

AF:

0.00803

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

116

174

232

290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0112

Hom.:

Bravo

AF:

0.00760

TwinsUK

AF:

0.00998

AC:

ALSPAC

AF:

0.0106

AC:

ESP6500AA

AF:

0.00297

AC:

ESP6500EA

AF:

0.00982

AC:

ExAC

AF:

0.00641

AC:

773

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial temporal lobe epilepsy 8 (1)

GAL-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.27

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0037

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.63

PhyloP100

-0.012

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-2.1

REVEL

Benign

0.022

Sift

Benign

0.074

Sift4G

Benign

0.21

Polyphen

0.0040

Vest4

0.29

MVP

0.27

MPC

0.12

ClinPred

0.0035

GERP RS

-0.28

PromoterAI

-0.051

Neutral

(source)

Varity_R

0.051

gMVP

0.47

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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