rs61759527
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_012064.4(MIP):c.-10C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 1,613,542 control chromosomes in the GnomAD database, including 382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.016 ( 36 hom., cov: 32)
Exomes 𝑓: 0.019 ( 346 hom. )
Consequence
MIP
NM_012064.4 5_prime_UTR
NM_012064.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.54
Genes affected
MIP (HGNC:7103): (major intrinsic protein of lens fiber) Major intrinsic protein is a member of the water-transporting aquaporins as well as the original member of the MIP family of channel proteins. The function of the fiber cell membrane protein encoded by this gene is undetermined, yet this protein is speculated to play a role in intracellular communication. The MIP protein is expressed in the ocular lens and is required for correct lens function. This gene has been mapped among aquaporins AQP2, AQP5, and AQP6, in a potential gene cluster at 12q13. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
Variant 12-56454623-G-T is Benign according to our data. Variant chr12-56454623-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 309889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-56454623-G-T is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.016 (2442/152308) while in subpopulation NFE AF= 0.0227 (1543/68026). AF 95% confidence interval is 0.0217. There are 36 homozygotes in gnomad4. There are 1253 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 2442 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MIP | NM_012064.4 | c.-10C>A | 5_prime_UTR_variant | 1/4 | ENST00000652304.1 | NP_036196.1 | ||
MIP | XM_011538354.2 | c.76-868C>A | intron_variant | XP_011536656.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MIP | ENST00000652304.1 | c.-10C>A | 5_prime_UTR_variant | 1/4 | NM_012064.4 | ENSP00000498622 | P1 | |||
MIP | ENST00000555551.1 | n.317-868C>A | intron_variant, non_coding_transcript_variant | 1 | ||||||
MIP | ENST00000648442.1 | n.494-868C>A | intron_variant, non_coding_transcript_variant | |||||||
MIP | ENST00000650166.1 | n.250-868C>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0160 AC: 2441AN: 152190Hom.: 36 Cov.: 32
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GnomAD3 exomes AF: 0.0169 AC: 4255AN: 251184Hom.: 48 AF XY: 0.0176 AC XY: 2395AN XY: 135762
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GnomAD4 exome AF: 0.0193 AC: 28186AN: 1461234Hom.: 346 Cov.: 33 AF XY: 0.0194 AC XY: 14069AN XY: 726930
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GnomAD4 genome AF: 0.0160 AC: 2442AN: 152308Hom.: 36 Cov.: 32 AF XY: 0.0168 AC XY: 1253AN XY: 74474
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 31, 2018 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Cataract 15 multiple types Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | 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. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at