5-147824670-C-T

Variant names:

• chr5-147824670-C-T
• rs34809998
• NM_001379610.1:c.231G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001379610.1(SPINK1):​c.231G>A​(p.Gly77Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,613,948 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G77G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0075 (16 hom., cov: 33)
  • Exomes 𝑓: 0.00084 (20 hom.)
• Consequence: SPINK1 NM_001379610.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.19
• Publications: 3 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=-0.49).
• BP6: Variant 5-147824670-C-T is Benign according to our data. Variant chr5-147824670-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.19 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00746 (1136/152190) while in subpopulation AFR AF = 0.0265 (1101/41522). AF 95% confidence interval is 0.0252. There are 16 homozygotes in GnomAd4. There are 557 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1136 AD,Unknown gene.

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.231G>A	p.Gly77Gly	synonymous	Exon 4 of 4	NP_001366539.1	P00995
	SPINK1	NM_001354966.2		c.231G>A	p.Gly77Gly	synonymous	Exon 5 of 5	NP_001341895.1	P00995
	SPINK1	NM_003122.5		c.231G>A	p.Gly77Gly	synonymous	Exon 5 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.231G>A	p.Gly77Gly	synonymous	Exon 4 of 4	ENSP00000296695.5	P00995
	SPINK1	ENST00000505722.1	TSL:2	n.146G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.00746 AC: 1135 AN: 152072 Hom.: 16 Cov.: 33

Gnomad AFR AF: 0.0266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00184 AC: 461 AN: 250748 AF XY: 0.00130

Gnomad AFR exome AF: 0.0263

Gnomad AMR exome AF: 0.000753

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.000654

GnomAD4 exome AF: 0.000840 AC: 1228 AN: 1461758 Hom.: 20 Cov.: 31 AF XY: 0.000699 AC XY: 508 AN XY: 727184

African (AFR) AF: 0.0312 AC: 1044 AN: 33474

American (AMR) AF: 0.00110 AC: 49 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111946

Other (OTH) AF: 0.00176 AC: 106 AN: 60386

GnomAD4 genome AF: 0.00746 AC: 1136 AN: 152190 Hom.: 16 Cov.: 33 AF XY: 0.00749 AC XY: 557 AN XY: 74402

African (AFR) AF: 0.0265 AC: 1101 AN: 41522

American (AMR) AF: 0.00164 AC: 25 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68020

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00380 Hom.: 9

Bravo AF: 0.00901

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Hereditary pancreatitis (4)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.39
DANN	Benign	0.35
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

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: rs34809998; hg19: chr5-147204233;