19-56182251-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033106.4(GALP):​c.216C>G​(p.Ile72Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 1,608,358 control chromosomes in the GnomAD database, including 100,043 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict 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 0.34 (9111 hom., cov: 31)
  • Exomes 𝑓: 0.35 (90932 hom.)
• Consequence: GALP NM_033106.4 missense, splice_region
• Scores: Splicing: ADA: 0.0007041
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005278021).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

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>G	p.Ile72Met	missense splice_region	Exon 4 of 6	NP_149097.1
	GALP	NM_001145546.2		c.*17C>G		splice_region	Exon 3 of 5	NP_001139018.1
	GALP	NM_001145546.2		c.*17C>G		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>G	p.Ile72Met	missense splice_region	Exon 4 of 6	ENSP00000349884.2
	GALP	ENST00000440823.1	TSL:5	c.*17C>G		splice_region	Exon 3 of 5	ENSP00000411521.1
	GALP	ENST00000440823.1	TSL:5	c.*17C>G		3_prime_UTR	Exon 3 of 5	ENSP00000411521.1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52124 AN: 151838 Hom.: 9108 Cov.: 31

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.358

GnomAD2 exomes AF: 0.338 AC: 84876 AN: 250948 AF XY: 0.342

Gnomad AFR exome AF: 0.341

Gnomad AMR exome AF: 0.327

Gnomad ASJ exome AF: 0.313

Gnomad EAS exome AF: 0.218

Gnomad FIN exome AF: 0.315

Gnomad NFE exome AF: 0.363

Gnomad OTH exome AF: 0.341

GnomAD4 exome AF: 0.351 AC: 511175 AN: 1456402 Hom.: 90932 Cov.: 30 AF XY: 0.351 AC XY: 254677 AN XY: 724878

African (AFR) AF: 0.336 AC: 11221 AN: 33376

American (AMR) AF: 0.326 AC: 14562 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 7963 AN: 26088

East Asian (EAS) AF: 0.219 AC: 8703 AN: 39662

South Asian (SAS) AF: 0.361 AC: 31066 AN: 86118

European-Finnish (FIN) AF: 0.323 AC: 17237 AN: 53386

Middle Eastern (MID) AF: 0.290 AC: 1669 AN: 5756

European-Non Finnish (NFE) AF: 0.360 AC: 398265 AN: 1107148

Other (OTH) AF: 0.340 AC: 20489 AN: 60204

GnomAD4 genome AF: 0.343 AC: 52165 AN: 151956 Hom.: 9111 Cov.: 31 AF XY: 0.341 AC XY: 25309 AN XY: 74262

African (AFR) AF: 0.342 AC: 14161 AN: 41448

American (AMR) AF: 0.329 AC: 5018 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1035 AN: 3464

East Asian (EAS) AF: 0.213 AC: 1099 AN: 5150

South Asian (SAS) AF: 0.336 AC: 1617 AN: 4818

European-Finnish (FIN) AF: 0.316 AC: 3331 AN: 10550

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24644 AN: 67950

Other (OTH) AF: 0.360 AC: 762 AN: 2114

Alfa AF: 0.331 Hom.: 5252

Bravo AF: 0.345

TwinsUK AF: 0.350 AC: 1297

ALSPAC AF: 0.371 AC: 1430

ESP6500AA AF: 0.340 AC: 1496

ESP6500EA AF: 0.362 AC: 3109

ExAC AF: 0.343 AC: 41683

EpiCase AF: 0.367

EpiControl AF: 0.360

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.2
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.0053	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.023
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.91	P
Vest4		0.054
MPC		0.20
ClinPred		0.041	T
GERP RS		-2.4
Varity_R		0.19
gMVP		0.17
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00070
dbscSNV1_RF	Benign	0.028
SpliceAI score (max)		0.030		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; COSMIC: COSV61999231; COSMIC: COSV61999231;