chr11-68691002-T-C

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
• Publications: 30 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 -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAL	NM_015973.5	MANE Select	c.*15T>C		3_prime_UTR	Exon 6 of 6	NP_057057.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAL	ENST00000265643.4	TSL:1 MANE Select	c.*15T>C		3_prime_UTR	Exon 6 of 6	ENSP00000265643.3	P22466
	GAL	ENST00000933457.1		c.*15T>C		3_prime_UTR	Exon 7 of 7	ENSP00000603516.1
	GAL	ENST00000933456.1		c.*15T>C		3_prime_UTR	Exon 6 of 6	ENSP00000603515.1

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

African (AFR) AF: 0.428 AC: 13850 AN: 32346

American (AMR) AF: 0.711 AC: 31734 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 17378 AN: 25746

East Asian (EAS) AF: 0.768 AC: 30292 AN: 39430

South Asian (SAS) AF: 0.637 AC: 54292 AN: 85170

European-Finnish (FIN) AF: 0.870 AC: 46044 AN: 52940

Middle Eastern (MID) AF: 0.517 AC: 2926 AN: 5662

European-Non Finnish (NFE) AF: 0.654 AC: 694080 AN: 1060732

Other (OTH) 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

African (AFR) AF: 0.435 AC: 18033 AN: 41450

American (AMR) AF: 0.667 AC: 10191 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2349 AN: 3472

East Asian (EAS) AF: 0.780 AC: 4031 AN: 5168

South Asian (SAS) AF: 0.652 AC: 3146 AN: 4822

European-Finnish (FIN) AF: 0.884 AC: 9372 AN: 10596

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.665 AC: 45188 AN: 67988

Other (OTH) AF: 0.615 AC: 1299 AN: 2112

Alfa AF: 0.642 Hom.: 100563

Bravo AF: 0.593

Asia WGS AF: 0.710 AC: 2469 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Familial temporal lobe epilepsy 8 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.16
DANN	Benign	0.35
PhyloP100		-2.5
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

Other links and lift over

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