rs8102476

chr19-38244973-C-T

Variant summary

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

The ENST00000590510.5(SPINT2):c.-45+839C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,804 control chromosomes in the GnomAD database, including 13,965 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 0.41 (13965 hom., cov: 31)
• Consequence: SPINT2 ENST00000590510.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

Genes affected

SPINT2 (HGNC:11247): (serine peptidase inhibitor, Kunitz type 2) This gene encodes a transmembrane protein with two extracellular Kunitz domains that inhibits a variety of serine proteases. The protein inhibits HGF activator which prevents the formation of active hepatocyte growth factor. This gene is a putative tumor suppressor, and mutations in this gene result in congenital sodium diarrhea. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPINT2	ENST00000590510.5	c.-45+839C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62211 AN: 151686 Hom.: 13959 Cov.: 31

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.410 AC: 62270 AN: 151804 Hom.: 13965 Cov.: 31 AF XY: 0.421 AC XY: 31265 AN XY: 74198

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.382

Alfa AF: 0.442 Hom.: 33142

Bravo AF: 0.392

Asia WGS AF: 0.578 AC: 2004 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.91
Dann	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8102476; hg19: chr19-38735613;