rs17658212

Positions:

• chr15-40853721-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_003710.4(SPINT1):​c.753C>T​(p.Leu251Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0535 in 1,614,104 control chromosomes in the GnomAD database, including 2,720 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 0.041 (171 hom., cov: 32)
  • Exomes 𝑓: 0.055 (2549 hom.)
• Consequence: SPINT1 NM_003710.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.723

Genes affected

SPINT1 (HGNC:11246): (serine peptidase inhibitor, Kunitz type 1) The protein encoded by this gene is a member of the Kunitz family of serine protease inhibitors. The protein is a potent inhibitor specific for HGF activator and is thought to be involved in the regulation of the proteolytic activation of HGF in injured tissues. Alternative splicing results in multiple variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPINT1	NM_003710.4	c.753C>T	p.Leu251Leu	synonymous_variant	5/11	ENST00000562057.6	NP_003701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPINT1	ENST00000562057.6	c.753C>T	p.Leu251Leu	synonymous_variant	5/11	1	NM_003710.4	ENSP00000457076.1

Frequencies

GnomAD3 genomes AF: 0.0410 AC: 6238 AN: 152218 Hom.: 170 Cov.: 32

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0496

Gnomad ASJ AF: 0.0724

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0126

Gnomad FIN AF: 0.0279

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0617

Gnomad OTH AF: 0.0617

GnomAD3 exomes AF: 0.0418 AC: 10493 AN: 251198 Hom.: 285 AF XY: 0.0425 AC XY: 5770 AN XY: 135780

Gnomad AFR exome AF: 0.0113

Gnomad AMR exome AF: 0.0375

Gnomad ASJ exome AF: 0.0625

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0144

Gnomad FIN exome AF: 0.0284

Gnomad NFE exome AF: 0.0616

Gnomad OTH exome AF: 0.0535

GnomAD4 exome AF: 0.0548 AC: 80104 AN: 1461768 Hom.: 2549 Cov.: 33 AF XY: 0.0542 AC XY: 39421 AN XY: 727170

Gnomad4 AFR exome AF: 0.00962

Gnomad4 AMR exome AF: 0.0405

Gnomad4 ASJ exome AF: 0.0646

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0153

Gnomad4 FIN exome AF: 0.0270

Gnomad4 NFE exome AF: 0.0630

Gnomad4 OTH exome AF: 0.0513

GnomAD4 genome AF: 0.0409 AC: 6238 AN: 152336 Hom.: 171 Cov.: 32 AF XY: 0.0388 AC XY: 2892 AN XY: 74496

Gnomad4 AFR AF: 0.0121

Gnomad4 AMR AF: 0.0495

Gnomad4 ASJ AF: 0.0724

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0130

Gnomad4 FIN AF: 0.0279

Gnomad4 NFE AF: 0.0617

Gnomad4 OTH AF: 0.0611

Alfa AF: 0.0594 Hom.: 386

Bravo AF: 0.0427

Asia WGS AF: 0.00779 AC: 27 AN: 3478

EpiCase AF: 0.0690

EpiControl AF: 0.0666

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.7
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.36		Position offset: 13

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

Publications

LitVar

Other links and lift over

dbSNP: rs17658212; hg19: chr15-41145919;