rs3860974

chr9-33231887-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPINK4	ENST00000379725.5	c.130+10779T>C		intron_variant		3

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

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.824

Gnomad4 ASJ AF: 0.841

Gnomad4 EAS AF: 0.865

Gnomad4 SAS AF: 0.793

Gnomad4 FIN AF: 0.866

Gnomad4 NFE AF: 0.841

Gnomad4 OTH AF: 0.748

Alfa AF: 0.809 Hom.: 22978

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3860974; hg19: chr9-33231885;