Variant chr5-147824629-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001379610.1(SPINK1):c.*32C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.05 in 1,607,666 control chromosomes in the GnomAD database, including 3,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 382 hom., cov: 32)

Exomes 𝑓: 0.050 ( 3423 hom. )

Consequence

SPINK1
NM_001379610.1 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0630

Variant links:

Genes affected

SPINK1 (HGNC:11244): (serine peptidase inhibitor Kazal type 1) The protein encoded by this gene is a trypsin inhibitor, which is secreted from pancreatic acinar cells into pancreatic juice. It is thought to function in the prevention of trypsin-catalyzed premature activation of zymogens within the pancreas and the pancreatic duct. Mutations in this gene are associated with hereditary pancreatitis and tropical calcific pancreatitis. [provided by RefSeq, Oct 2008]

SPINK1 links:

SPINK1 (HGNC:):

SPINK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 5-147824629-G-A is Benign according to our data. Variant chr5-147824629-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 351510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-147824629-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPINK1	NM_001379610.1 linkuse as main transcript	c.*32C>T		3_prime_UTR_variant	4/4	ENST00000296695.10	NP_001366539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPINK1	ENST00000296695 linkuse as main transcript	c.*32C>T		3_prime_UTR_variant	4/4	1	NM_001379610.1	ENSP00000296695.5		P00995
SPINK1	ENST00000505722.1 linkuse as main transcript	n.187C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0521

AC:

7926

AN:

152054

Hom.:

382

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0184

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.0329

Gnomad EAS

AF:

0.0847

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0378

Gnomad OTH

AF:

0.0493

GnomAD3 exomes

AF:

0.0831

AC:

20816

AN:

250526

Hom.:

1515

AF XY:

0.0809

AC XY:

10960

AN XY:

135420

show subpopulations

Gnomad AFR exome

AF:

0.0170

Gnomad AMR exome

AF:

0.206

Gnomad ASJ exome

AF:

0.0282

Gnomad EAS exome

AF:

0.0789

Gnomad SAS exome

AF:

0.156

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.0381

Gnomad OTH exome

AF:

0.0717

GnomAD4 exome

AF:

0.0498

AC:

72492

AN:

1455494

Hom.:

3423

Cov.:

AF XY:

0.0522

AC XY:

37784

AN XY:

724478

show subpopulations

Gnomad4 AFR exome

AF:

0.0155

Gnomad4 AMR exome

AF:

0.203

Gnomad4 ASJ exome

AF:

0.0333

Gnomad4 EAS exome

AF:

0.0799

Gnomad4 SAS exome

AF:

0.153

Gnomad4 FIN exome

AF:

0.100

Gnomad4 NFE exome

AF:

0.0335

Gnomad4 OTH exome

AF:

0.0504

GnomAD4 genome

AF:

0.0521

AC:

7933

AN:

152172

Hom.:

382

Cov.:

AF XY:

0.0597

AC XY:

4439

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0187

Gnomad4 AMR

AF:

0.136

Gnomad4 ASJ

AF:

0.0329

Gnomad4 EAS

AF:

0.0846

Gnomad4 SAS

AF:

0.158

Gnomad4 FIN

AF:

0.103

Gnomad4 NFE

AF:

0.0377

Gnomad4 OTH

AF:

0.0488

Alfa

AF:

0.0415

Hom.:

257

Bravo

AF:

0.0510

Asia WGS

AF:

0.106

AC:

369

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 21, 2018	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Apr 20, 2020	- -

Hereditary pancreatitis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.6

DANN

Benign

0.57

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over