12-6377490-T-C

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.223
Variant links:
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
LTBRNM_001270987.2 linkuse as main transcriptc.39+1896T>C intron_variant NP_001257916.1
LTBRNM_001414309.1 linkuse as main transcriptc.39+1896T>C intron_variant NP_001401238.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SCNN1AENST00000536788.1 linkuse as main transcriptc.9+177A>G intron_variant 4 ENSP00000443434
LTBRENST00000539925.5 linkuse as main transcriptc.39+1896T>C intron_variant 2 ENSP00000440875 A2P36941-2
SCNN1AENST00000538957.1 linkuse as main transcriptn.23-139A>G intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
AF:
0.175
AC:
26592
AN:
152056
Hom.:
2681
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0965
Gnomad AMI
AF:
0.295
Gnomad AMR
AF:
0.148
Gnomad ASJ
AF:
0.135
Gnomad EAS
AF:
0.0736
Gnomad SAS
AF:
0.228
Gnomad FIN
AF:
0.264
Gnomad MID
AF:
0.117
Gnomad NFE
AF:
0.220
Gnomad OTH
AF:
0.143
GnomAD4 exome
AF:
0.203
AC:
103365
AN:
509072
Hom.:
11532
AF XY:
0.204
AC XY:
54478
AN XY:
267230
show subpopulations
Gnomad4 AFR exome
AF:
0.0951
Gnomad4 AMR exome
AF:
0.151
Gnomad4 ASJ exome
AF:
0.123
Gnomad4 EAS exome
AF:
0.0649
Gnomad4 SAS exome
AF:
0.224
Gnomad4 FIN exome
AF:
0.261
Gnomad4 NFE exome
AF:
0.223
Gnomad4 OTH exome
AF:
0.177
GnomAD4 genome
AF:
0.175
AC:
26605
AN:
152174
Hom.:
2680
Cov.:
32
AF XY:
0.176
AC XY:
13105
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.0966
Gnomad4 AMR
AF:
0.148
Gnomad4 ASJ
AF:
0.135
Gnomad4 EAS
AF:
0.0736
Gnomad4 SAS
AF:
0.227
Gnomad4 FIN
AF:
0.264
Gnomad4 NFE
AF:
0.220
Gnomad4 OTH
AF:
0.142
Alfa
AF:
0.200
Hom.:
865
Bravo
AF:
0.161
Asia WGS
AF:
0.136
AC:
474
AN:
3478

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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxSep 04, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
1.6
DANN
Benign
0.16

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs879605; hg19: chr12-6486656; API