rs1042577

Variant names:

• chr11-68691002-T-C
• rs1042577
• NM_015973.5:c.*15T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• 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

Our verdict: Benign. The variant received -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
GAL	NM_015973.5	c.*15T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000265643.4	NP_057057.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAL	ENST00000265643.4	c.*15T>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_015973.5	ENSP00000265643.3

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

GnomAD2 exomes AF: 0.683 AC: 171367 AN: 250952 AF XY: 0.682

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 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 AC: 13850 AN: 32346

Gnomad4 AMR exome AF: 0.711 AC: 31734 AN: 44638

Gnomad4 ASJ exome AF: 0.675 AC: 17378 AN: 25746

Gnomad4 EAS exome AF: 0.768 AC: 30292 AN: 39430

Gnomad4 SAS exome AF: 0.637 AC: 54292 AN: 85170

Gnomad4 FIN exome AF: 0.870 AC: 46044 AN: 52940

Gnomad4 NFE exome AF: 0.654 AC: 694080 AN: 1060732

Gnomad4 Remaining exome AF: 0.648 AC: 37921 AN: 58562

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 AC: 0.435054 AN: 0.435054

Gnomad4 AMR AF: 0.667 AC: 0.66695 AN: 0.66695

Gnomad4 ASJ AF: 0.677 AC: 0.676555 AN: 0.676555

Gnomad4 EAS AF: 0.780 AC: 0.779992 AN: 0.779992

Gnomad4 SAS AF: 0.652 AC: 0.652426 AN: 0.652426

Gnomad4 FIN AF: 0.884 AC: 0.884485 AN: 0.884485

Gnomad4 NFE AF: 0.665 AC: 0.664647 AN: 0.664647

Gnomad4 OTH AF: 0.615 AC: 0.615057 AN: 0.615057

Alfa AF: 0.642 Hom.: 100563

Bravo AF: 0.593

Asia WGS AF: 0.710 AC: 2469 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Familial temporal lobe epilepsy 8 Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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
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

Publications

LitVar

Other links and lift over

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