rs104894244
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_153766.3(KCNJ1):c.180C>T(p.Tyr60Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,614,140 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00075 ( 3 hom., cov: 32)
Exomes 𝑓: 0.000049 ( 1 hom. )
Consequence
KCNJ1
NM_153766.3 synonymous
NM_153766.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.21
Genes affected
KCNJ1 (HGNC:6255): (potassium inwardly rectifying channel subfamily J member 1) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. It is activated by internal ATP and probably plays an important role in potassium homeostasis. The encoded protein has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Mutations in this gene have been associated with antenatal Bartter syndrome, which is characterized by salt wasting, hypokalemic alkalosis, hypercalciuria, and low blood pressure. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 11-128840064-G-A is Benign according to our data. Variant chr11-128840064-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 376831.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
BP7
Synonymous conserved (PhyloP=3.21 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000749 (114/152282) while in subpopulation AMR AF= 0.00745 (114/15302). AF 95% confidence interval is 0.00634. There are 3 homozygotes in gnomad4. There are 90 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNJ1 | NM_153766.3 | c.180C>T | p.Tyr60Tyr | synonymous_variant | 3/3 | ENST00000392666.6 | NP_722450.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNJ1 | ENST00000392666.6 | c.180C>T | p.Tyr60Tyr | synonymous_variant | 3/3 | 1 | NM_153766.3 | ENSP00000376434.1 |
Frequencies
GnomAD3 genomes AF: 0.000749 AC: 114AN: 152164Hom.: 3 Cov.: 32
GnomAD3 genomes
AF:
AC:
114
AN:
152164
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000275 AC: 69AN: 251326Hom.: 1 AF XY: 0.000250 AC XY: 34AN XY: 135824
GnomAD3 exomes
AF:
AC:
69
AN:
251326
Hom.:
AF XY:
AC XY:
34
AN XY:
135824
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000493 AC: 72AN: 1461858Hom.: 1 Cov.: 33 AF XY: 0.0000481 AC XY: 35AN XY: 727234
GnomAD4 exome
AF:
AC:
72
AN:
1461858
Hom.:
Cov.:
33
AF XY:
AC XY:
35
AN XY:
727234
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000749 AC: 114AN: 152282Hom.: 3 Cov.: 32 AF XY: 0.00121 AC XY: 90AN XY: 74454
GnomAD4 genome
AF:
AC:
114
AN:
152282
Hom.:
Cov.:
32
AF XY:
AC XY:
90
AN XY:
74454
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 18, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Sep 28, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at