15-40857481-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003710.4. 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
	SPINT1	NM_003710.4	MANE Select	c.*506A>G		3_prime_UTR	Exon 11 of 11	NP_003701.1	O43278-2
	SPINT1	NM_001386873.1		c.*506A>G		3_prime_UTR	Exon 11 of 11	NP_001373802.1	O43278-1
	SPINT1	NM_181642.3		c.*506A>G		3_prime_UTR	Exon 11 of 11	NP_857593.1	O43278-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINT1	ENST00000562057.6	TSL:1 MANE Select	c.*506A>G		3_prime_UTR	Exon 11 of 11	ENSP00000457076.1	O43278-2
	SPINT1	ENST00000344051.8	TSL:1	c.*506A>G		3_prime_UTR	Exon 11 of 11	ENSP00000342098.4	O43278-1
	SPINT1	ENST00000920945.1		c.*506A>G		3_prime_UTR	Exon 11 of 11	ENSP00000591004.1

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

African (AFR) AF: 0.143 AC: 4 AN: 28

American (AMR) AF: 0.822 AC: 97 AN: 118

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 20 AN: 26

East Asian (EAS) AF: 0.682 AC: 30 AN: 44

South Asian (SAS) AF: 0.777 AC: 185 AN: 238

European-Finnish (FIN) AF: 0.750 AC: 24 AN: 32

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.807 AC: 892 AN: 1106

Other (OTH) AF: 0.757 AC: 56 AN: 74

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

African (AFR) AF: 0.302 AC: 12532 AN: 41446

American (AMR) AF: 0.782 AC: 11950 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 2799 AN: 3472

East Asian (EAS) AF: 0.787 AC: 4047 AN: 5140

South Asian (SAS) AF: 0.768 AC: 3704 AN: 4824

European-Finnish (FIN) AF: 0.840 AC: 8897 AN: 10590

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54111 AN: 67978

Other (OTH) AF: 0.696 AC: 1471 AN: 2114

Alfa AF: 0.740 Hom.: 14629

Bravo AF: 0.642

Asia WGS AF: 0.741 AC: 2577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.53
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17649; hg19: chr15-41149679;