chr10-113588989-CCTT-C
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBS1BS2
The NM_198060.4(NRAP):c.5176_5178del(p.Lys1726del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00171 in 1,613,520 control chromosomes in the GnomAD database, including 37 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0085 ( 12 hom., cov: 32)
Exomes 𝑓: 0.0010 ( 25 hom. )
Consequence
NRAP
NM_198060.4 inframe_deletion
NM_198060.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.93
Genes affected
NRAP (HGNC:7988): (nebulin related anchoring protein) Predicted to enable actin filament binding activity and muscle alpha-actinin binding activity. Predicted to be involved in cardiac muscle thin filament assembly. Predicted to be located in fascia adherens; muscle tendon junction; and myofibril. Predicted to be active in Z disc. [provided by Alliance of Genome Resources, Apr 2022]
HABP2 (HGNC:4798): (hyaluronan binding protein 2) This gene encodes a member of the peptidase S1 family of serine proteases. The encoded preproprotein is secreted by hepatocytes and proteolytically processed to generate heavy and light chains that form the mature heterodimer. Further autoproteolysis leads to smaller, inactive peptides. This extracellular protease binds hyaluronic acid and may play a role in the coagulation and fibrinolysis systems. Mutations in this gene are associated with nonmedullary thyroid cancer and susceptibility to venous thromboembolism. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_198060.4. Strenght limited to Supporting due to length of the change: 1aa.
BP6
?
Variant 10-113588989-CCTT-C is Benign according to our data. Variant chr10-113588989-CCTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 298931.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00847 (1289/152218) while in subpopulation AFR AF= 0.0288 (1195/41518). AF 95% confidence interval is 0.0274. There are 12 homozygotes in gnomad4. There are 596 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 12 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NRAP | NM_198060.4 | c.5176_5178del | p.Lys1726del | inframe_deletion | 42/42 | ENST00000359988.4 | |
HABP2 | NM_004132.5 | c.*627_*629del | 3_prime_UTR_variant | 13/13 | ENST00000351270.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NRAP | ENST00000359988.4 | c.5176_5178del | p.Lys1726del | inframe_deletion | 42/42 | 1 | NM_198060.4 | A1 | |
HABP2 | ENST00000351270.4 | c.*627_*629del | 3_prime_UTR_variant | 13/13 | 1 | NM_004132.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00845 AC: 1286AN: 152100Hom.: 12 Cov.: 32
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GnomAD3 exomes AF: 0.00235 AC: 585AN: 249242Hom.: 9 AF XY: 0.00168 AC XY: 226AN XY: 134890
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GnomAD4 exome AF: 0.00101 AC: 1478AN: 1461302Hom.: 25 AF XY: 0.000876 AC XY: 637AN XY: 727000
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GnomAD4 genome ? AF: 0.00847 AC: 1289AN: 152218Hom.: 12 Cov.: 32 AF XY: 0.00801 AC XY: 596AN XY: 74418
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
NRAP-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 01, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Factor VII Marburg I Variant Thrombophilia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at