11-68685517-G-T

Variant names:

• chr11-68685517-G-T
• rs694066
• NM_015973.5:c.82-77G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015973.5(GAL):​c.82-77G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000012 in 833,562 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: GAL NM_015973.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 0 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)

LOC107984343 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAL	NM_015973.5	MANE Select	c.82-77G>T		intron	N/A	NP_057057.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAL	ENST00000265643.4	TSL:1 MANE Select	c.82-77G>T		intron	N/A	ENSP00000265643.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000120 AC: 1 AN: 833562 Hom.: 0 AF XY: 0.00000228 AC XY: 1 AN XY: 438212

African (AFR) AF: 0.00 AC: 0 AN: 21332

American (AMR) AF: 0.00 AC: 0 AN: 41744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22042

East Asian (EAS) AF: 0.00 AC: 0 AN: 35924

South Asian (SAS) AF: 0.0000139 AC: 1 AN: 71840

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4566

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 544222

Other (OTH) AF: 0.00 AC: 0 AN: 39712

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.26
DANN	Benign	0.70
PhyloP100		-1.5

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: rs694066; hg19: chr11-68452985;