rs35737774

Variant names:

• chr5-147828042-G-A
• rs35737774
• NM_001379610.1:c.174C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-147828042-G-A
• chr5-147828042-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001379610.1(SPINK1):​c.174C>T​(p.Cys58Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00748 in 1,612,588 control chromosomes in the GnomAD database, including 755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (417 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (338 hom.)
• Consequence: SPINK1 NM_001379610.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.0340
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• hereditary chronic pancreatitis

  Inheritance: AD, Unknown Classification: STRONG, MODERATE, SUPPORTIVE, NO_KNOWN Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-147828042-G-A is Benign according to our data. Variant chr5-147828042-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258913.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.034 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379610.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINK1	NM_001379610.1	MANE Select	c.174C>T	p.Cys58Cys	synonymous	Exon 3 of 4	NP_001366539.1	P00995
	SPINK1	NM_001354966.2		c.174C>T	p.Cys58Cys	synonymous	Exon 4 of 5	NP_001341895.1	P00995
	SPINK1	NM_003122.5		c.174C>T	p.Cys58Cys	synonymous	Exon 4 of 5	NP_003113.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINK1	ENST00000296695.10	TSL:1 MANE Select	c.174C>T	p.Cys58Cys	synonymous	Exon 3 of 4	ENSP00000296695.5	P00995
	SPINK1	ENST00000510027.2	TSL:3	c.174C>T	p.Cys58Cys	synonymous	Exon 3 of 3	ENSP00000427376.1	D6RIU5
	SPINK1	ENST00000505722.1	TSL:2	n.89C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0410 AC: 6237 AN: 151942 Hom.: 417 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.0311

GnomAD2 exomes AF: 0.0108 AC: 2708 AN: 250228 AF XY: 0.00796

Gnomad AFR exome AF: 0.146

Gnomad AMR exome AF: 0.00768

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000935

Gnomad NFE exome AF: 0.000301

Gnomad OTH exome AF: 0.00639

GnomAD4 exome AF: 0.00398 AC: 5819 AN: 1460528 Hom.: 338 Cov.: 30 AF XY: 0.00346 AC XY: 2514 AN XY: 726630

African (AFR) AF: 0.135 AC: 4513 AN: 33426

American (AMR) AF: 0.00868 AC: 388 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26106

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39560

South Asian (SAS) AF: 0.000302 AC: 26 AN: 86198

European-Finnish (FIN) AF: 0.0000754 AC: 4 AN: 53068

Middle Eastern (MID) AF: 0.00539 AC: 31 AN: 5752

European-Non Finnish (NFE) AF: 0.000265 AC: 294 AN: 1111380

Other (OTH) AF: 0.00928 AC: 560 AN: 60338

GnomAD4 genome AF: 0.0410 AC: 6242 AN: 152060 Hom.: 417 Cov.: 32 AF XY: 0.0403 AC XY: 2999 AN XY: 74340

African (AFR) AF: 0.142 AC: 5887 AN: 41468

American (AMR) AF: 0.0163 AC: 249 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10558

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000530 AC: 36 AN: 67988

Other (OTH) AF: 0.0307 AC: 65 AN: 2114

Alfa AF: 0.0214 Hom.: 79

Bravo AF: 0.0477

Asia WGS AF: 0.0130 AC: 44 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Hereditary pancreatitis (4)
-	-	3	not provided (3)
-	-	3	not specified (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.28
PhyloP100		-0.034
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35737774; hg19: chr5-147207605;