11-68690475-C-T

Variant names:

• chr11-68690475-C-T
• rs3136541
• NM_015973.5:c.302-442C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015973.5(GAL):​c.302-442C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 151,938 control chromosomes in the GnomAD database, including 30,051 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 0.61 (30051 hom., cov: 31)
• Consequence: GAL NM_015973.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 11 publications found

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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAL	NM_015973.5	c.302-442C>T		intron_variant	Intron 5 of 5	ENST00000265643.4	NP_057057.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAL	ENST00000265643.4	c.302-442C>T		intron_variant	Intron 5 of 5	1	NM_015973.5	ENSP00000265643.3

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93380 AN: 151820 Hom.: 30044 Cov.: 31

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.607

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.615 AC: 93415 AN: 151938 Hom.: 30051 Cov.: 31 AF XY: 0.627 AC XY: 46620 AN XY: 74304

African (AFR) AF: 0.432 AC: 17875 AN: 41364

American (AMR) AF: 0.664 AC: 10132 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2339 AN: 3470

East Asian (EAS) AF: 0.780 AC: 4024 AN: 5160

South Asian (SAS) AF: 0.650 AC: 3132 AN: 4820

European-Finnish (FIN) AF: 0.874 AC: 9265 AN: 10596

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44738 AN: 67954

Other (OTH) AF: 0.609 AC: 1284 AN: 2108

Alfa AF: 0.622 Hom.: 4285

Bravo AF: 0.588

Asia WGS AF: 0.708 AC: 2462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.11
DANN	Benign	0.70
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3136541; hg19: chr11-68457943;