rs1042577

chr11-68691002-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015973.5(GAL):c.*15T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 1,557,318 control chromosomes in the GnomAD database, including 340,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (30650 hom., cov: 32)
  • Exomes 𝑓: 0.66 (309826 hom.)
• Consequence: GAL NM_015973.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.47

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-68691002-T-C is Benign according to our data. Variant chr11-68691002-T-C is described in ClinVar as [Benign]. Clinvar id is 1285292.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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/exons	MANE	UniProt
GAL	NM_015973.5	c.*15T>C		3_prime_UTR_variant	6/6	ENST00000265643.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAL	ENST00000265643.4	c.*15T>C		3_prime_UTR_variant	6/6	1	NM_015973.5	P1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94323 AN: 151974 Hom.: 30645 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.613

GnomAD3 exomes AF: 0.683 AC: 171367 AN: 250952 Hom.: 59884 AF XY: 0.682 AC XY: 92502 AN XY: 135720

Gnomad AFR exome AF: 0.429

Gnomad AMR exome AF: 0.715

Gnomad ASJ exome AF: 0.672

Gnomad EAS exome AF: 0.781

Gnomad SAS exome AF: 0.643

Gnomad FIN exome AF: 0.876

Gnomad NFE exome AF: 0.669

Gnomad OTH exome AF: 0.674

GnomAD4 exome AF: 0.661 AC: 928517 AN: 1405226 Hom.: 309826 Cov.: 25 AF XY: 0.660 AC XY: 463532 AN XY: 702288

Gnomad4 AFR exome AF: 0.428

Gnomad4 AMR exome AF: 0.711

Gnomad4 ASJ exome AF: 0.675

Gnomad4 EAS exome AF: 0.768

Gnomad4 SAS exome AF: 0.637

Gnomad4 FIN exome AF: 0.870

Gnomad4 NFE exome AF: 0.654

Gnomad4 OTH exome AF: 0.648

GnomAD4 genome AF: 0.620 AC: 94357 AN: 152092 Hom.: 30650 Cov.: 32 AF XY: 0.633 AC XY: 47062 AN XY: 74364

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.677

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.652

Gnomad4 FIN AF: 0.884

Gnomad4 NFE AF: 0.665

Gnomad4 OTH AF: 0.615

Alfa AF: 0.654 Hom.: 67994

Bravo AF: 0.593

Asia WGS AF: 0.710 AC: 2469 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial temporal lobe epilepsy 8 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.16
Dann	Benign	0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs1042577; hg19: chr11-68458470; COSMIC: COSV55764285;