chr18-45644160-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2
The NM_007163.4(SLC14A2):c.1351G>A(p.Gly451Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00074 in 1,614,086 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0035 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00045 ( 3 hom. )
Consequence
SLC14A2
NM_007163.4 missense, splice_region
NM_007163.4 missense, splice_region
Scores
1
5
9
Splicing: ADA: 1.000
2
Clinical Significance
Conservation
PhyloP100: 7.04
Genes affected
SLC14A2 (HGNC:10919): (solute carrier family 14 member 2) The protein encoded by this gene belongs to the urea transporter family. In mammalian cells, urea is the chief end product of nitrogen catabolism, and plays an important role in the urinary concentration mechanism. This protein is expressed in the inner medulla of the kidney, and mediates rapid transepithelial urea transport across the inner medullary collecting duct. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP6
Variant 18-45644160-G-A is Benign according to our data. Variant chr18-45644160-G-A is described in ClinVar as [Benign]. Clinvar id is 784378.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC14A2 | NM_007163.4 | c.1351G>A | p.Gly451Arg | missense_variant, splice_region_variant | 10/20 | ENST00000255226.11 | |
LOC105372093 | XR_935423.3 | n.873-7003C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC14A2 | ENST00000255226.11 | c.1351G>A | p.Gly451Arg | missense_variant, splice_region_variant | 10/20 | 1 | NM_007163.4 | P1 | |
SLC14A2 | ENST00000586448.5 | c.1351G>A | p.Gly451Arg | missense_variant, splice_region_variant | 11/21 | 2 | P1 | ||
SLC14A2 | ENST00000323329.3 | c.*673G>A | 3_prime_UTR_variant, NMD_transcript_variant | 11/11 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00351 AC: 534AN: 152184Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000972 AC: 244AN: 251058Hom.: 1 AF XY: 0.000840 AC XY: 114AN XY: 135672
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GnomAD4 exome AF: 0.000451 AC: 659AN: 1461784Hom.: 3 Cov.: 31 AF XY: 0.000384 AC XY: 279AN XY: 727196
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GnomAD4 genome AF: 0.00351 AC: 535AN: 152302Hom.: 2 Cov.: 32 AF XY: 0.00336 AC XY: 250AN XY: 74468
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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 | Invitae | Jul 10, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);
MVP
MPC
0.33
ClinPred
T
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Splicing
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Calibrated prediction
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 0
Find out detailed SpliceAI scores and Pangolin per-transcript scores at