5-147835557-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003122.5(SPINK1):c.-192+3577A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 151,944 control chromosomes in the GnomAD database, including 3,946 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 0.22 (3946 hom., cov: 32)
• Consequence: SPINK1 NM_003122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490

Genes affected

SPINK1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPINK1	NM_001354966.2	c.-225+3577A>C		intron_variant
SPINK1	NM_003122.5	c.-192+3577A>C		intron_variant
SPINK1	XM_047417625.1	c.-192+1206A>C		intron_variant
SPINK1	XM_047417626.1	c.-225+1206A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33047 AN: 151826 Hom.: 3944 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.212

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.218 AC: 33088 AN: 151944 Hom.: 3946 Cov.: 32 AF XY: 0.220 AC XY: 16356 AN XY: 74242

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.545

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.210

Alfa AF: 0.206 Hom.: 7191

Bravo AF: 0.225

Asia WGS AF: 0.401 AC: 1391 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	12
Dann	Benign	0.88

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4705204; hg19: chr5-147215120; COSMIC: COSV57024389;