NM_001692.4:c.481G>A
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_001692.4(ATP6V1B1):c.481G>A(p.Glu161Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.025 in 1,614,138 control chromosomes in the GnomAD database, including 794 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_001692.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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ATP6V1B1 | ENST00000234396.10 | c.481G>A | p.Glu161Lys | missense_variant | Exon 6 of 14 | 1 | NM_001692.4 | ENSP00000234396.4 | ||
ENSG00000258881 | ENST00000606025.5 | c.476-17541C>T | intron_variant | Intron 5 of 5 | 5 | ENSP00000475641.1 |
Frequencies
GnomAD3 genomes AF: 0.0260 AC: 3957AN: 152156Hom.: 65 Cov.: 32
GnomAD3 exomes AF: 0.0300 AC: 7535AN: 251352Hom.: 191 AF XY: 0.0334 AC XY: 4536AN XY: 135870
GnomAD4 exome AF: 0.0249 AC: 36452AN: 1461864Hom.: 729 Cov.: 32 AF XY: 0.0269 AC XY: 19550AN XY: 727238
GnomAD4 genome AF: 0.0260 AC: 3960AN: 152274Hom.: 65 Cov.: 32 AF XY: 0.0275 AC XY: 2050AN XY: 74442
ClinVar
Submissions by phenotype
Renal tubular acidosis with progressive nerve deafness Pathogenic:1Benign:4
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This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not specified Benign:5
Variant summary: ATP6V1B1 c.481G>A (p.Glu161Lys) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.03 in 251352 control chromosomes in the gnomAD database, including 191 homozygotes. The observed variant frequency is approximately 27-fold of the estimated maximal expected allele frequency for a pathogenic variant in ATP6V1B1 causing Renal Tubular Acidosis With Progressive Nerve Deafness phenotype (0.0011), strongly suggesting that the variant is benign. To our knowledge, no penetrant association of c.481G>A with Renal Tubular Acidosis With Progressive Nerve Deafness has been reported. Nine submitters have provided clinical-significance assessments for this variant to ClinVar after 2014. The majority classified the variant as benign (n=8), and one classified it as likely pathogenic. Based on the evidence outlined above, the variant was classified as benign. -
Glu161Lys in Exon 06 of ATP6V1B1: This variant is not expected to have clinical significance because it has been identified in 2.4% (90/3738) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs114234874). -
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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not provided Benign:3
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at