rs3860974

Variant names:

• chr9-33231887-T-C
• rs3860974
• ENST00000379725.5:c.130+10779T>C

Variant summary

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

The ENST00000379725.5(SPINK4):​c.130+10779T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 152,178 control chromosomes in the GnomAD database, including 43,321 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 0.73 (43321 hom., cov: 33)
• Consequence: SPINK4 ENST00000379725.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• Publications: 3 publications found

Genes affected

SPINK4 (HGNC:16646): (serine peptidase inhibitor Kazal type 4) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity and response to xenobiotic stimulus. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINK4	ENST00000379725.5	c.130+10779T>C		intron_variant	Intron 2 of 4	3		ENSP00000369048.1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111485 AN: 152060 Hom.: 43305 Cov.: 33

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.965

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.791

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.747

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.733 AC: 111536 AN: 152178 Hom.: 43321 Cov.: 33 AF XY: 0.740 AC XY: 55031 AN XY: 74400

African (AFR) AF: 0.449 AC: 18637 AN: 41466

American (AMR) AF: 0.824 AC: 12595 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2920 AN: 3470

East Asian (EAS) AF: 0.865 AC: 4482 AN: 5180

South Asian (SAS) AF: 0.793 AC: 3828 AN: 4830

European-Finnish (FIN) AF: 0.866 AC: 9183 AN: 10598

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.841 AC: 57225 AN: 68022

Other (OTH) AF: 0.748 AC: 1580 AN: 2112

Alfa AF: 0.811 Hom.: 25638

Bravo AF: 0.718

Asia WGS AF: 0.782 AC: 2722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.8
DANN	Benign	0.72
PhyloP100		-0.024
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3860974; hg19: chr9-33231885;