Variant chr12-56450565-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The NM_012064.4(MIP):c.*715G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,224 control chromosomes in the GnomAD database, including 9,439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.33 ( 9424 hom., cov: 32)

Exomes 𝑓: 0.38 ( 15 hom. )

Consequence

MIP
NM_012064.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.180

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]

MIP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP6

Variant 12-56450565-C-T is Benign according to our data. Variant chr12-56450565-C-T is described in ClinVar as [Benign]. Clinvar id is 309871.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
MIP	NM_012064.4 linkuse as main transcript	c.*715G>A	3_prime_UTR_variant	4/4	ENST00000652304.1
MIP	XM_011538354.2 linkuse as main transcript	c.*715G>A	3_prime_UTR_variant	6/6
MIP	XM_017019306.2 linkuse as main transcript	c.*715G>A	3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIP	ENST00000652304.1 linkuse as main transcript	c.*715G>A		3_prime_UTR_variant	4/4		NM_012064.4	P1

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49605

AN:

151968

Hom.:

9418

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.511

Gnomad AMR

AF:

0.288

Gnomad ASJ

AF:

0.324

Gnomad EAS

AF:

0.245

Gnomad SAS

AF:

0.430

Gnomad FIN

AF:

0.443

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.427

Gnomad OTH

AF:

0.295

GnomAD4 exome

AF:

0.377

AC:

AN:

138

Hom.:

Cov.:

AF XY:

0.293

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.125

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 SAS exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.430

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.326

AC:

49626

AN:

152086

Hom.:

9424

Cov.:

AF XY:

0.328

AC XY:

24403

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.141

Gnomad4 AMR

AF:

0.287

Gnomad4 ASJ

AF:

0.324

Gnomad4 EAS

AF:

0.246

Gnomad4 SAS

AF:

0.432

Gnomad4 FIN

AF:

0.443

Gnomad4 NFE

AF:

0.427

Gnomad4 OTH

AF:

0.298

Alfa

AF:

0.355

Hom.:

3763

Bravo

AF:

0.298

Asia WGS

AF:

0.348

AC:

1208

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 submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.81

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over