chr4-165873677-T-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_012464.5(TLL1):c.-228T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 519,492 control chromosomes in the GnomAD database, including 16,332 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.26 ( 7516 hom., cov: 32)
Exomes 𝑓: 0.18 ( 8816 hom. )
Consequence
TLL1
NM_012464.5 5_prime_UTR
NM_012464.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.948
Genes affected
TLL1 (HGNC:11843): (tolloid like 1) This gene encodes an astacin-like, zinc-dependent, metalloprotease that belongs to the peptidase M12A family. This protease processes procollagen C-propeptides, such as chordin, pro-biglycan and pro-lysyl oxidase. Studies in mice suggest that this gene plays multiple roles in the development of mammalian heart, and is essential for the formation of the interventricular septum. Allelic variants of this gene are associated with atrial septal defect type 6. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
Variant 4-165873677-T-C is Benign according to our data. Variant chr4-165873677-T-C is described in ClinVar as [Benign]. Clinvar id is 1240677.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TLL1 | NM_012464.5 | c.-228T>C | 5_prime_UTR_variant | 1/21 | ENST00000061240.7 | ||
TLL1 | NM_001204760.2 | c.-228T>C | 5_prime_UTR_variant | 1/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TLL1 | ENST00000061240.7 | c.-228T>C | 5_prime_UTR_variant | 1/21 | 1 | NM_012464.5 | P1 | ||
TLL1 | ENST00000507499.5 | c.-228T>C | 5_prime_UTR_variant | 1/22 | 1 | ||||
TLL1 | ENST00000509505.5 | c.-228T>C | 5_prime_UTR_variant, NMD_transcript_variant | 1/21 | 1 | ||||
TLL1 | ENST00000504560.5 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.263 AC: 39904AN: 151988Hom.: 7491 Cov.: 32
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GnomAD4 exome AF: 0.183 AC: 67395AN: 367388Hom.: 8816 Cov.: 3 AF XY: 0.186 AC XY: 35642AN XY: 191784
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GnomAD4 genome ? AF: 0.263 AC: 39981AN: 152104Hom.: 7516 Cov.: 32 AF XY: 0.263 AC XY: 19544AN XY: 74370
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at