rs3745833

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-56182251-C-A
• chr19-56182251-C-G
• chr19-56182251-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_033106.4(GALP):​c.216C>A​(p.Ile72Ile) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GALP NM_033106.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.0002120
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• Publications: 43 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-0.023 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033106.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALP	NM_033106.4	MANE Select	c.216C>A	p.Ile72Ile	splice_region synonymous	Exon 4 of 6	NP_149097.1
	GALP	NM_001145546.2		c.*17C>A		splice_region	Exon 3 of 5	NP_001139018.1
	GALP	NM_001145546.2		c.*17C>A		3_prime_UTR	Exon 3 of 5	NP_001139018.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALP	ENST00000357330.7	TSL:1 MANE Select	c.216C>A	p.Ile72Ile	splice_region synonymous	Exon 4 of 6	ENSP00000349884.2
	GALP	ENST00000440823.1	TSL:5	c.*17C>A		splice_region	Exon 3 of 5	ENSP00000411521.1
	GALP	ENST00000440823.1	TSL:5	c.*17C>A		3_prime_UTR	Exon 3 of 5	ENSP00000411521.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459446 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726202

African (AFR) AF: 0.00 AC: 0 AN: 33430

American (AMR) AF: 0.00 AC: 0 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109864

Other (OTH) AF: 0.00 AC: 0 AN: 60312

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.7
DANN	Benign	0.57
PhyloP100		-0.023

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00021
dbscSNV1_RF	Benign	0.12
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: rs3745833; hg19: chr19-56693620;