4-56821138-A-G

Position:

• chr4-56821138-A-G

Variant summary

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

The NM_001271718.2(SPINK2):​c.205+320T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 152,094 control chromosomes in the GnomAD database, including 19,386 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 0.48 (19386 hom., cov: 33)
• Consequence: SPINK2 NM_001271718.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289

Genes affected

SPINK2 (HGNC:11245): (serine peptidase inhibitor Kazal type 2) This gene encodes a member of the family of serine protease inhibitors of the Kazal type (SPINK). The encoded protein acts as a trypsin and acrosin inhibitor in the genital tract and is localized in the spermatozoa. The protein has been associated with the progression of lymphomas. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPINK2	NM_001271718.2	c.205+320T>C		intron_variant		ENST00000506738.6	NP_001258647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPINK2	ENST00000506738.6	c.205+320T>C		intron_variant		2	NM_001271718.2	ENSP00000425961	A2

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73352 AN: 151976 Hom.: 19336 Cov.: 33

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.483 AC: 73463 AN: 152094 Hom.: 19386 Cov.: 33 AF XY: 0.483 AC XY: 35890 AN XY: 74356

Gnomad4 AFR AF: 0.707

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.466

Alfa AF: 0.404 Hom.: 26141

Bravo AF: 0.504

Asia WGS AF: 0.483 AC: 1679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.3
DANN	Benign	0.32

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: rs781542; hg19: chr4-57687304;