11-113690190-A-C

Variant names:

• chr11-113690190-A-C
• rs753267452
• NM_030770.4:c.1206+41T>G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_030770.4(TMPRSS5):​c.1206+41T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.044 (0 hom., cov: 0)
  • Exomes 𝑓: 0.098 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMPRSS5 NM_030770.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.72

Genes affected

TMPRSS5 (HGNC:14908): (transmembrane serine protease 5) This gene encodes a protein that belongs to the serine protease family. Serine proteases are known to be involved in many physiological and pathological processes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-113690190-A-C is Benign according to our data. Variant chr11-113690190-A-C is described in ClinVar as [Benign]. Clinvar id is 675054.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS5	NM_030770.4	c.1206+41T>G		intron_variant	Intron 11 of 12	ENST00000299882.11	NP_110397.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS5	ENST00000299882.11	c.1206+41T>G		intron_variant	Intron 11 of 12	1	NM_030770.4	ENSP00000299882.5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 706 AN: 16224 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0443

Gnomad AMI AF: 0.0857

Gnomad AMR AF: 0.0393

Gnomad ASJ AF: 0.0226

Gnomad EAS AF: 0.0221

Gnomad SAS AF: 0.0270

Gnomad FIN AF: 0.0550

Gnomad MID AF: 0.0313

Gnomad NFE AF: 0.0455

Gnomad OTH AF: 0.0489

GnomAD3 exomes AF: 0.322 AC: 6424 AN: 19972 Hom.: 0 AF XY: 0.355 AC XY: 4021 AN XY: 11326

Gnomad AFR exome AF: 0.0362

Gnomad AMR exome AF: 0.255

Gnomad ASJ exome AF: 0.408

Gnomad EAS exome AF: 0.0515

Gnomad SAS exome AF: 0.419

Gnomad FIN exome AF: 0.358

Gnomad NFE exome AF: 0.304

Gnomad OTH exome AF: 0.324

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0978 AC: 16639 AN: 170126 Hom.: 0 Cov.: 3 AF XY: 0.101 AC XY: 8982 AN XY: 88860

Gnomad4 AFR exome AF: 0.0652

Gnomad4 AMR exome AF: 0.0852

Gnomad4 ASJ exome AF: 0.0700

Gnomad4 EAS exome AF: 0.0362

Gnomad4 SAS exome AF: 0.124

Gnomad4 FIN exome AF: 0.0605

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.0816

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0437 AC: 710 AN: 16262 Hom.: 0 Cov.: 0 AF XY: 0.0425 AC XY: 348 AN XY: 8188

Gnomad4 AFR AF: 0.0447

Gnomad4 AMR AF: 0.0391

Gnomad4 ASJ AF: 0.0226

Gnomad4 EAS AF: 0.0243

Gnomad4 SAS AF: 0.0269

Gnomad4 FIN AF: 0.0550

Gnomad4 NFE AF: 0.0455

Gnomad4 OTH AF: 0.0484

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.71

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: rs753267452; hg19: chr11-113560912;