rs694066

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-68685517-G-A
• chr11-68685517-G-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.82-77G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0922 in 985,366 control chromosomes in the GnomAD database, including 6,241 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 0.14 (2478 hom., cov: 33)
  • Exomes 𝑓: 0.083 (3763 hom.)
• Consequence: GAL NM_015973.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 19 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

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>A		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>A		intron	N/A	ENSP00000265643.3

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21521 AN: 152140 Hom.: 2473 Cov.: 33

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0846

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.0198

Gnomad SAS AF: 0.0531

Gnomad FIN AF: 0.0228

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0849

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.0832 AC: 69275 AN: 833108 Hom.: 3763 AF XY: 0.0819 AC XY: 35857 AN XY: 437990

African (AFR) AF: 0.321 AC: 6845 AN: 21308

American (AMR) AF: 0.0603 AC: 2517 AN: 41732

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 2336 AN: 22032

East Asian (EAS) AF: 0.0157 AC: 564 AN: 35924

South Asian (SAS) AF: 0.0649 AC: 4659 AN: 71832

European-Finnish (FIN) AF: 0.0313 AC: 1633 AN: 52176

Middle Eastern (MID) AF: 0.151 AC: 689 AN: 4566

European-Non Finnish (NFE) AF: 0.0848 AC: 46106 AN: 543848

Other (OTH) AF: 0.0989 AC: 3926 AN: 39690

GnomAD4 genome AF: 0.141 AC: 21544 AN: 152258 Hom.: 2478 Cov.: 33 AF XY: 0.136 AC XY: 10105 AN XY: 74446

African (AFR) AF: 0.316 AC: 13102 AN: 41526

American (AMR) AF: 0.0845 AC: 1293 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 396 AN: 3470

East Asian (EAS) AF: 0.0199 AC: 103 AN: 5184

South Asian (SAS) AF: 0.0528 AC: 255 AN: 4834

European-Finnish (FIN) AF: 0.0228 AC: 242 AN: 10612

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0849 AC: 5775 AN: 68014

Other (OTH) AF: 0.125 AC: 263 AN: 2112

Alfa AF: 0.133 Hom.: 354

Bravo AF: 0.154

Asia WGS AF: 0.0610 AC: 213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.56
DANN	Benign	0.76
PhyloP100		-1.5
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: rs694066; hg19: chr11-68452985;