4-56812976-A-G

Position:

• chr4-56812976-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.250-1182T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,140 control chromosomes in the GnomAD database, including 41,312 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 (41312 hom., cov: 32)
• Consequence: SPINK2 NM_001271718.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.862

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPINK2	NM_001271718.2	c.250-1182T>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.250-1182T>C		intron_variant		2	NM_001271718.2	ENSP00000425961	A2

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110640 AN: 152022 Hom.: 41251 Cov.: 32

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.728 AC: 110761 AN: 152140 Hom.: 41312 Cov.: 32 AF XY: 0.735 AC XY: 54646 AN XY: 74380

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.741

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.973

Gnomad4 SAS AF: 0.841

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.636

Gnomad4 OTH AF: 0.718

Alfa AF: 0.668 Hom.: 14773

Bravo AF: 0.737

Asia WGS AF: 0.897 AC: 3115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.54
DANN	Benign	0.38

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: rs10015630; hg19: chr4-57679142;