15-40857481-A-G

Variant names:

• chr15-40857481-A-G
• rs17649
• NM_003710.4:c.*506A>G

Variant summary

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

The NM_003710.4(SPINT1):​c.*506A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 153,720 control chromosomes in the GnomAD database, including 37,543 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 0.66 (37012 hom., cov: 32)
  • Exomes 𝑓: 0.79 (531 hom.)
• Consequence: SPINT1 NM_003710.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.976

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPINT1	NM_003710.4	c.*506A>G		3_prime_UTR_variant	Exon 11 of 11	ENST00000562057.6	NP_003701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINT1	ENST00000562057.6	c.*506A>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_003710.4	ENSP00000457076.1
SPINT1	ENST00000344051.8	c.*506A>G		3_prime_UTR_variant	Exon 11 of 11	1		ENSP00000342098.4

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100467 AN: 151936 Hom.: 37006 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.781

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.692

GnomAD4 exome AF: 0.785 AC: 1308 AN: 1666 Hom.: 531 Cov.: 0 AF XY: 0.790 AC XY: 746 AN XY: 944

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.822

Gnomad4 ASJ exome AF: 0.769

Gnomad4 EAS exome AF: 0.682

Gnomad4 SAS exome AF: 0.777

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.807

Gnomad4 OTH exome AF: 0.757

GnomAD4 genome AF: 0.661 AC: 100486 AN: 152054 Hom.: 37012 Cov.: 32 AF XY: 0.668 AC XY: 49674 AN XY: 74316

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.782

Gnomad4 ASJ AF: 0.806

Gnomad4 EAS AF: 0.787

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.840

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.696

Alfa AF: 0.739 Hom.: 8600

Bravo AF: 0.642

Asia WGS AF: 0.741 AC: 2577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs17649; hg19: chr15-41149679;