chr11-130188097-C-T

Variant names:

• chr11-130188097-C-T
• rs55833552
• NM_021978.4:c.82-17C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_021978.4(ST14):​c.82-17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00217 in 1,613,626 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (33 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (33 hom.)
• Consequence: ST14 NM_021978.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00700
• Publications: 0 publications found

Genes affected

ST14 (HGNC:11344): (ST14 transmembrane serine protease matriptase) The protein encoded by this gene is an epithelial-derived, integral membrane serine protease. This protease forms a complex with the Kunitz-type serine protease inhibitor, HAI-1, and is found to be activated by sphingosine 1-phosphate. This protease has been shown to cleave and activate hepatocyte growth factor/scattering factor, and urokinase plasminogen activator, which suggest the function of this protease as an epithelial membrane activator for other proteases and latent growth factors. The expression of this protease has been associated with breast, colon, prostate, and ovarian tumors, which implicates its role in cancer invasion, and metastasis. [provided by RefSeq, Jul 2008]

ST14 Gene-Disease associations (from GenCC):

• autosomal recessive congenital ichthyosis 11

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-130188097-C-T is Benign according to our data. Variant chr11-130188097-C-T is described in ClinVar as Benign. ClinVar VariationId is 3020566.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0112 (1711/152194) while in subpopulation AFR AF = 0.0393 (1630/41524). AF 95% confidence interval is 0.0377. There are 33 homozygotes in GnomAd4. There are 813 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021978.4. 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
	ST14	NM_021978.4	MANE Select	c.82-17C>T		intron	N/A	NP_068813.1	Q9Y5Y6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST14	ENST00000278742.6	TSL:1 MANE Select	c.82-17C>T		intron	N/A	ENSP00000278742.5	Q9Y5Y6
	ST14	ENST00000894129.1		c.82-17C>T		intron	N/A	ENSP00000564188.1
	ST14	ENST00000894128.1		c.82-17C>T		intron	N/A	ENSP00000564187.1

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1688 AN: 152076 Hom.: 31 Cov.: 33

Gnomad AFR AF: 0.0391

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00862

GnomAD2 exomes AF: 0.00302 AC: 753 AN: 249284 AF XY: 0.00239

Gnomad AFR exome AF: 0.0397

Gnomad AMR exome AF: 0.00122

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00122 AC: 1783 AN: 1461432 Hom.: 33 Cov.: 32 AF XY: 0.00109 AC XY: 794 AN XY: 727004

African (AFR) AF: 0.0406 AC: 1359 AN: 33466

American (AMR) AF: 0.00145 AC: 65 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39682

South Asian (SAS) AF: 0.00117 AC: 101 AN: 86212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53308

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5768

European-Non Finnish (NFE) AF: 0.0000765 AC: 85 AN: 1111826

Other (OTH) AF: 0.00258 AC: 156 AN: 60366

GnomAD4 genome AF: 0.0112 AC: 1711 AN: 152194 Hom.: 33 Cov.: 33 AF XY: 0.0109 AC XY: 813 AN XY: 74416

African (AFR) AF: 0.0393 AC: 1630 AN: 41524

American (AMR) AF: 0.00235 AC: 36 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5160

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67998

Other (OTH) AF: 0.0147 AC: 31 AN: 2110

Alfa AF: 0.00488 Hom.: 6

Bravo AF: 0.0119

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.57
PhyloP100		0.0070
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: rs55833552; hg19: chr11-130057992;