19-56182251-C-T

Variant names:

• chr19-56182251-C-T
• rs3745833
• NM_033106.4:c.216C>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_033106.4(GALP):​c.216C>T​(p.Ile72Ile) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,611,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: GALP NM_033106.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.0005910
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230

Genes affected

GALP (HGNC:24840): (galanin like peptide) This gene encodes a member of the galanin family of neuropeptides. The encoded protein binds galanin receptors 1, 2 and 3 with the highest affinity for galanin receptor 3 and has been implicated in biological processes involving the central nervous system including hypothalamic regulation of metabolism and reproduction. A peptide encoded by a splice variant of this gene, termed alarin, has vasoactive properties, displays antimicrobial activity against E. coli, and may serve as a marker for neuroblastic tumors.[provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=-0.023 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALP	NM_033106.4	c.216C>T	p.Ile72Ile	splice_region_variant, synonymous_variant	Exon 4 of 6	ENST00000357330.7	NP_149097.1
GALP	NM_001145546.2	c.*17C>T		splice_region_variant	Exon 3 of 5		NP_001139018.1
GALP	NM_001145546.2	c.*17C>T		3_prime_UTR_variant	Exon 3 of 5		NP_001139018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALP	ENST00000357330.7	c.216C>T	p.Ile72Ile	splice_region_variant, synonymous_variant	Exon 4 of 6	1	NM_033106.4	ENSP00000349884.2
GALP	ENST00000440823.1	c.*17C>T		splice_region_variant	Exon 3 of 5	5		ENSP00000411521.1
GALP	ENST00000440823.1	c.*17C>T		3_prime_UTR_variant	Exon 3 of 5	5		ENSP00000411521.1
GALP	ENST00000590002.1	c.*17C>T		downstream_gene_variant		1		ENSP00000464698.1

Frequencies

GnomAD3 genomes AF: 0.0000856 AC: 13 AN: 151906 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000159 AC: 40 AN: 250948 Hom.: 0 AF XY: 0.000177 AC XY: 24 AN XY: 135624

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000784

Gnomad FIN exome AF: 0.0000926

Gnomad NFE exome AF: 0.0000881

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000108 AC: 158 AN: 1459446 Hom.: 0 Cov.: 30 AF XY: 0.000131 AC XY: 95 AN XY: 726202

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.0000448

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000893

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.0000613

Gnomad4 OTH exome AF: 0.0000829

GnomAD4 genome AF: 0.0000855 AC: 13 AN: 152024 Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 8 AN XY: 74294

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.0000111 Hom.: 5252

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.6
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00059
dbscSNV1_RF	Benign	0.21
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

Publications

LitVar

Other links and lift over

dbSNP: rs3745833; hg19: chr19-56693620;