rs6032474

chr20-45725733-G-A

Variant summary

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

The NM_178455.3(SPINT4):c.*98G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 1,481,854 control chromosomes in the GnomAD database, including 124,947 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 0.46 (17977 hom., cov: 32)
  • Exomes 𝑓: 0.39 (106970 hom.)
• Consequence: SPINT4 NM_178455.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158

Genes affected

SPINT4 (HGNC:16130): (serine peptidase inhibitor, Kunitz type 4) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPINT4	NM_178455.3	c.*98G>A		3_prime_UTR_variant	3/3	ENST00000279058.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPINT4	ENST00000279058.4	c.*98G>A		3_prime_UTR_variant	3/3	1	NM_178455.3	P1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70394 AN: 151792 Hom.: 17955 Cov.: 32

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.471

GnomAD4 exome AF: 0.391 AC: 519537 AN: 1329944 Hom.: 106970 Cov.: 19 AF XY: 0.396 AC XY: 264642 AN XY: 667456

Gnomad4 AFR exome AF: 0.686

Gnomad4 AMR exome AF: 0.291

Gnomad4 ASJ exome AF: 0.548

Gnomad4 EAS exome AF: 0.461

Gnomad4 SAS exome AF: 0.547

Gnomad4 FIN exome AF: 0.386

Gnomad4 NFE exome AF: 0.363

Gnomad4 OTH exome AF: 0.431

GnomAD4 genome AF: 0.464 AC: 70454 AN: 151910 Hom.: 17977 Cov.: 32 AF XY: 0.465 AC XY: 34522 AN XY: 74232

Gnomad4 AFR AF: 0.673

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.469

Alfa AF: 0.392 Hom.: 22396

Bravo AF: 0.468

Asia WGS AF: 0.493 AC: 1715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.2
Dann	Benign	0.31

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: rs6032474; hg19: chr20-44354372; COSMIC: COSV54143276;