12-6377490-T-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001270987.2(LTBR):c.39+1896T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 661,246 control chromosomes in the GnomAD database, including 14,212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.17 ( 2680 hom., cov: 32)
Exomes 𝑓: 0.20 ( 11532 hom. )
Consequence
LTBR
NM_001270987.2 intron
NM_001270987.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.223
Genes affected
LTBR (HGNC:6718): (lymphotoxin beta receptor) This gene encodes a member of the tumor necrosis factor receptor superfamily. The major ligands of this receptor include lymphotoxin alpha/beta and tumor necrosis factor ligand superfamily member 14. The encoded protein plays a role in signalling during the development of lymphoid and other organs, lipid metabolism, immune response, and programmed cell death. Activity of this receptor has also been linked to carcinogenesis. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Aug 2012]
SCNN1A (HGNC:10599): (sodium channel epithelial 1 subunit alpha) Nonvoltage-gated, amiloride-sensitive, sodium channels control fluid and electrolyte transport across epithelia in many organs. These channels are heteromeric complexes consisting of 3 subunits: alpha, beta, and gamma. This gene encodes the alpha subunit, and mutations in this gene have been associated with pseudohypoaldosteronism type 1 (PHA1), a rare salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 12-6377490-T-C is Benign according to our data. Variant chr12-6377490-T-C is described in ClinVar as [Benign]. Clinvar id is 1242331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LTBR | NM_001270987.2 | c.39+1896T>C | intron_variant | NP_001257916.1 | ||||
LTBR | NM_001414309.1 | c.39+1896T>C | intron_variant | NP_001401238.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCNN1A | ENST00000536788.1 | c.9+177A>G | intron_variant | 4 | ENSP00000443434 | |||||
LTBR | ENST00000539925.5 | c.39+1896T>C | intron_variant | 2 | ENSP00000440875 | A2 | ||||
SCNN1A | ENST00000538957.1 | n.23-139A>G | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.175 AC: 26592AN: 152056Hom.: 2681 Cov.: 32
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GnomAD4 exome AF: 0.203 AC: 103365AN: 509072Hom.: 11532 AF XY: 0.204 AC XY: 54478AN XY: 267230
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GnomAD4 genome AF: 0.175 AC: 26605AN: 152174Hom.: 2680 Cov.: 32 AF XY: 0.176 AC XY: 13105AN XY: 74412
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 04, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at