12-56450789-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_012064.4(MIP):​c.*491A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 167,844 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 30)
Exomes 𝑓: 0.0023 ( 0 hom. )

Consequence

MIP
NM_012064.4 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.153
Variant links:
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 -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 12-56450789-T-G is Benign according to our data. Variant chr12-56450789-T-G is described in ClinVar as [Benign]. Clinvar id is 309876.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00221 (336/152242) while in subpopulation AMR AF= 0.00425 (65/15290). AF 95% confidence interval is 0.00342. There are 1 homozygotes in gnomad4. There are 159 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
High AC in GnomAd4 at 336 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MIPNM_012064.4 linkuse as main transcriptc.*491A>C 3_prime_UTR_variant 4/4 ENST00000652304.1 NP_036196.1
MIPXM_011538354.2 linkuse as main transcriptc.*491A>C 3_prime_UTR_variant 6/6 XP_011536656.1
MIPXM_017019306.2 linkuse as main transcriptc.*491A>C 3_prime_UTR_variant 4/4 XP_016874795.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MIPENST00000652304.1 linkuse as main transcriptc.*491A>C 3_prime_UTR_variant 4/4 NM_012064.4 ENSP00000498622 P1

Frequencies

GnomAD3 genomes
AF:
0.00221
AC:
336
AN:
152124
Hom.:
1
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.000773
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00426
Gnomad ASJ
AF:
0.00202
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00104
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00312
Gnomad OTH
AF:
0.00334
GnomAD4 exome
AF:
0.00231
AC:
36
AN:
15602
Hom.:
0
Cov.:
0
AF XY:
0.00177
AC XY:
15
AN XY:
8474
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00419
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000434
Gnomad4 FIN exome
AF:
0.00551
Gnomad4 NFE exome
AF:
0.00243
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00221
AC:
336
AN:
152242
Hom.:
1
Cov.:
30
AF XY:
0.00214
AC XY:
159
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.000771
Gnomad4 AMR
AF:
0.00425
Gnomad4 ASJ
AF:
0.00202
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00104
Gnomad4 NFE
AF:
0.00312
Gnomad4 OTH
AF:
0.00331
Alfa
AF:
0.00276
Hom.:
0
Bravo
AF:
0.00258
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Cataract 15 multiple types Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
CADD
Benign
5.1
DANN
Benign
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: rs137926387; hg19: chr12-56844573; API