rs7101947

Variant names:

• chr11-68684660-C-T
• rs7101947
• NM_015973.5:c.-73C>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.-73C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 342,652 control chromosomes in the GnomAD database, including 82,738 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 0.64 (32840 hom., cov: 32)
  • Exomes 𝑓: 0.72 (49898 hom.)
• Consequence: GAL NM_015973.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 7 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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAL	NM_015973.5	c.-73C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	ENST00000265643.4	NP_057057.2
GAL	NM_015973.5	c.-73C>T		5_prime_UTR_variant	Exon 1 of 6	ENST00000265643.4	NP_057057.2
LOC107984343	XR_001748281.1	n.230+3181G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAL	ENST00000265643.4	c.-73C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	1	NM_015973.5	ENSP00000265643.3
GAL	ENST00000265643.4	c.-73C>T		5_prime_UTR_variant	Exon 1 of 6	1	NM_015973.5	ENSP00000265643.3
GAL	ENST00000538401.1	n.*22C>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97404 AN: 151506 Hom.: 32830 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.858

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.641

GnomAD4 exome AF: 0.717 AC: 136990 AN: 191040 Hom.: 49898 Cov.: 0 AF XY: 0.717 AC XY: 70296 AN XY: 98034

African (AFR) AF: 0.426 AC: 2290 AN: 5378

American (AMR) AF: 0.742 AC: 3994 AN: 5380

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 5311 AN: 7038

East Asian (EAS) AF: 0.793 AC: 13623 AN: 17178

South Asian (SAS) AF: 0.752 AC: 2637 AN: 3508

European-Finnish (FIN) AF: 0.850 AC: 13740 AN: 16156

Middle Eastern (MID) AF: 0.683 AC: 676 AN: 990

European-Non Finnish (NFE) AF: 0.701 AC: 86119 AN: 122936

Other (OTH) AF: 0.689 AC: 8600 AN: 12476

GnomAD4 genome AF: 0.643 AC: 97433 AN: 151612 Hom.: 32840 Cov.: 32 AF XY: 0.654 AC XY: 48450 AN XY: 74090

African (AFR) AF: 0.425 AC: 17606 AN: 41378

American (AMR) AF: 0.703 AC: 10730 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2593 AN: 3464

East Asian (EAS) AF: 0.804 AC: 4092 AN: 5092

South Asian (SAS) AF: 0.744 AC: 3585 AN: 4818

European-Finnish (FIN) AF: 0.858 AC: 9034 AN: 10530

Middle Eastern (MID) AF: 0.678 AC: 198 AN: 292

European-Non Finnish (NFE) AF: 0.702 AC: 47566 AN: 67774

Other (OTH) AF: 0.645 AC: 1356 AN: 2102

Alfa AF: 0.665 Hom.: 4303

Bravo AF: 0.619

Asia WGS AF: 0.741 AC: 2542 AN: 3430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.1
DANN	Benign	0.85
PhyloP100		-1.9
PromoterAI		-0.040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=299/1	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: rs7101947; hg19: chr11-68452128; COSMIC: COSV55763948; COSMIC: COSV55763948;