rs706109

Positions:

• chr9-33240670-G-A

Variant summary

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

The NM_014471.3(SPINK4):​c.61+401G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,032 control chromosomes in the GnomAD database, including 12,111 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 0.35 (12111 hom., cov: 32)
• Consequence: SPINK4 NM_014471.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPINK4	NM_014471.3	c.61+401G>A		intron_variant		ENST00000379721.4	NP_055286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPINK4	ENST00000379721.4	c.61+401G>A		intron_variant		1	NM_014471.3	ENSP00000369045.3
SPINK4	ENST00000379725.5	c.131-4442G>A		intron_variant		3		ENSP00000369048.1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53692 AN: 151914 Hom.: 12100 Cov.: 32

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.354 AC: 53754 AN: 152032 Hom.: 12111 Cov.: 32 AF XY: 0.348 AC XY: 25875 AN XY: 74326

Gnomad4 AFR AF: 0.646

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.330

Alfa AF: 0.315 Hom.: 1142

Bravo AF: 0.372

Asia WGS AF: 0.326 AC: 1133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.56

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: rs706109; hg19: chr9-33240668;