chr11-68688942-T-C

Variant names:

• chr11-68688942-T-C
• rs3136540
• NM_015973.5:c.301+16T>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.301+16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 1,207,036 control chromosomes in the GnomAD database, including 330,269 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (40005 hom., cov: 32)
  • Exomes 𝑓: 0.74 (290264 hom.)
• Consequence: GAL NM_015973.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.245
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 11-68688942-T-C is Benign according to our data. Variant chr11-68688942-T-C is described in ClinVar as Benign. ClinVar VariationId is 1285291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.833 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.301+16T>C		intron	N/A	NP_057057.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAL	ENST00000265643.4	TSL:1 MANE Select	c.301+16T>C		intron	N/A	ENSP00000265643.3	P22466
	GAL	ENST00000933457.1		c.499+16T>C		intron	N/A	ENSP00000603516.1
	GAL	ENST00000933456.1		c.355+16T>C		intron	N/A	ENSP00000603515.1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109473 AN: 151992 Hom.: 39974 Cov.: 32

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.905

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.716

GnomAD2 exomes AF: 0.764 AC: 189041 AN: 247436 AF XY: 0.765

Gnomad AFR exome AF: 0.604

Gnomad AMR exome AF: 0.783

Gnomad ASJ exome AF: 0.757

Gnomad EAS exome AF: 0.845

Gnomad FIN exome AF: 0.897

Gnomad NFE exome AF: 0.740

Gnomad OTH exome AF: 0.754

GnomAD4 exome AF: 0.739 AC: 779785 AN: 1054926 Hom.: 290264 Cov.: 15 AF XY: 0.741 AC XY: 402106 AN XY: 542526

African (AFR) AF: 0.595 AC: 15514 AN: 26066

American (AMR) AF: 0.780 AC: 34296 AN: 43970

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 17809 AN: 23554

East Asian (EAS) AF: 0.846 AC: 32044 AN: 37890

South Asian (SAS) AF: 0.770 AC: 59889 AN: 77758

European-Finnish (FIN) AF: 0.893 AC: 47265 AN: 52948

Middle Eastern (MID) AF: 0.678 AC: 3391 AN: 5002

European-Non Finnish (NFE) AF: 0.722 AC: 535029 AN: 740956

Other (OTH) AF: 0.738 AC: 34548 AN: 46782

GnomAD4 genome AF: 0.720 AC: 109553 AN: 152110 Hom.: 40005 Cov.: 32 AF XY: 0.730 AC XY: 54286 AN XY: 74384

African (AFR) AF: 0.611 AC: 25310 AN: 41452

American (AMR) AF: 0.739 AC: 11302 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.759 AC: 2634 AN: 3472

East Asian (EAS) AF: 0.854 AC: 4421 AN: 5174

South Asian (SAS) AF: 0.786 AC: 3787 AN: 4816

European-Finnish (FIN) AF: 0.905 AC: 9604 AN: 10608

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.737 AC: 50076 AN: 67986

Other (OTH) AF: 0.717 AC: 1513 AN: 2110

Alfa AF: 0.717 Hom.: 14633

Bravo AF: 0.700

Asia WGS AF: 0.811 AC: 2820 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Familial temporal lobe epilepsy 8 (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.4
DANN	Benign	0.34
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3136540; hg19: chr11-68456410;