20-45749938-T-C

Variant names:

• chr20-45749938-T-C
• rs380421
• ENST00000448174.2:n.134T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000448174.2(SPINT5P):​n.134T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 169,542 control chromosomes in the GnomAD database, including 31,651 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 0.61 (28559 hom., cov: 32)
  • Exomes 𝑓: 0.59 (3092 hom.)
• Consequence: SPINT5P ENST00000448174.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339
• Publications: 18 publications found

Genes affected

SPINT5P (HGNC:16161): (serine peptidase inhibitor, Kunitz type 5, pseudogene)

WFDC3 (HGNC:15957): (WAP four-disulfide core domain 3) This gene encodes a member of the WAP-type four-disulfide core (WFDC) domain family. The WFDC domain, or WAP signature motif, contains eight cysteines forming four disulfide bonds at the core of the protein, and functions as a protease inhibitor. The encoded protein contains four WFDC domains. Most WFDC genes are localized to chromosome 20q12-q13 in two clusters: centromeric and telomeric. This gene belongs to the telomeric cluster. Alternatively spliced transcript variants have been observed but their full-length nature has not been determined. [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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000448174.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINT5P	ENST00000448174.2		n.134T>C		non_coding_transcript_exon	Exon 2 of 2
	WFDC3	ENST00000481847.5	TSL:5	n.520-1524A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92475 AN: 151796 Hom.: 28516 Cov.: 32

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.579

GnomAD4 exome AF: 0.586 AC: 10334 AN: 17628 Hom.: 3092 Cov.: 0 AF XY: 0.591 AC XY: 4971 AN XY: 8412

African (AFR) AF: 0.588 AC: 47 AN: 80

American (AMR) AF: 0.778 AC: 14 AN: 18

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 2 AN: 4

East Asian (EAS) AF: 0.333 AC: 2 AN: 6

South Asian (SAS) AF: 0.415 AC: 39 AN: 94

European-Finnish (FIN) AF: 0.602 AC: 8995 AN: 14946

Middle Eastern (MID) AF: 0.448 AC: 734 AN: 1638

European-Non Finnish (NFE) AF: 0.600 AC: 234 AN: 390

Other (OTH) AF: 0.591 AC: 267 AN: 452

GnomAD4 genome AF: 0.609 AC: 92579 AN: 151914 Hom.: 28559 Cov.: 32 AF XY: 0.605 AC XY: 44917 AN XY: 74250

African (AFR) AF: 0.580 AC: 24033 AN: 41406

American (AMR) AF: 0.682 AC: 10400 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1617 AN: 3472

East Asian (EAS) AF: 0.510 AC: 2636 AN: 5170

South Asian (SAS) AF: 0.454 AC: 2187 AN: 4822

European-Finnish (FIN) AF: 0.608 AC: 6437 AN: 10584

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.636 AC: 43214 AN: 67896

Other (OTH) AF: 0.580 AC: 1222 AN: 2108

Alfa AF: 0.617 Hom.: 24310

Bravo AF: 0.615

Asia WGS AF: 0.525 AC: 1828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.0
DANN	Benign	0.82
PhyloP100		-0.34

Splicing

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

Other links and lift over

dbSNP: rs380421; hg19: chr20-44378577; COSMIC: COSV71391138;