rs8102476

Variant names:

• chr19-38244973-C-T
• rs8102476
• ENST00000590510.5:c.-45+839C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 113 publications found

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]

SPINT2 Gene-Disease associations (from GenCC):

• syndromic congenital sodium diarrhea

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• congenital secretory sodium diarrhea 3

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000590510.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINT2	ENST00000590510.5	TSL:3	c.-45+839C>T		intron	N/A	ENSP00000465301.1	K7EJS4

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

African (AFR) AF: 0.246 AC: 10184 AN: 41382

American (AMR) AF: 0.453 AC: 6895 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1310 AN: 3468

East Asian (EAS) AF: 0.646 AC: 3327 AN: 5152

South Asian (SAS) AF: 0.558 AC: 2683 AN: 4808

European-Finnish (FIN) AF: 0.586 AC: 6183 AN: 10548

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30541 AN: 67906

Other (OTH) AF: 0.382 AC: 805 AN: 2110

Alfa AF: 0.436 Hom.: 66568

Bravo AF: 0.392

Asia WGS AF: 0.578 AC: 2004 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.91
DANN	Benign	0.45
PhyloP100		-2.0

Splicing

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

Other links and lift over

dbSNP: rs8102476; hg19: chr19-38735613;