11-68684970-C-T

Position:

chr11-68684970-C-T

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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 links:

LOC107984343 (HGNC:):

LOC107984343 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 475915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1187 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAL	NM_015973.5 linkuse as main transcript	c.47C>T	p.Ala16Val	missense_variant	2/6	ENST00000265643.4	NP_057057.2
LOC107984343	XR_001748281.1 linkuse as main transcript	n.230+2871G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAL	ENST00000265643.4 linkuse as main transcript	c.47C>T	p.Ala16Val	missense_variant	2/6	1	NM_015973.5	ENSP00000265643	P1

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

GnomAD3 exomes

AF:

0.00681

AC:

1586

AN:

232814

Hom.:

AF XY:

0.00667

AC XY:

850

AN XY:

127484

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 SAS exome

AF:

0.000745

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

Gnomad4 AFR exome

AF:

0.00177

Gnomad4 AMR exome

AF:

0.00383

Gnomad4 ASJ exome

AF:

0.0178

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.000820

Gnomad4 FIN exome

AF:

0.00901

Gnomad4 NFE exome

AF:

0.0107

Gnomad4 OTH exome

AF:

0.00841

GnomAD4 genome

AF:

0.00779

AC:

1187

AN:

152338

Hom.:

Cov.:

AF XY:

0.00714

AC XY:

532

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00216

Gnomad4 AMR

AF:

0.00549

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00696

Gnomad4 NFE

AF:

0.0117

Gnomad4 OTH

AF:

0.00803

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

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

GAL-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 21, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Familial temporal lobe epilepsy 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

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

MutationTaster

Benign

1.0

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

Varity_R

0.051

gMVP

0.47

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over