12-56450109-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000648304.1(ENSG00000285528):n.*1587C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 151,612 control chromosomes in the GnomAD database, including 11,165 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11165 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ENSG00000285528
ENST00000648304.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.219

Publications

9 publications found

Variant links:

Genes affected

ENSG00000285528 (HGNC:):

ENSG00000285528 links:

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 Gene-Disease associations (from GenCC):

cataract 15 multiple types
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
cerulean cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
early-onset lamellar cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
early-onset nuclear cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
early-onset posterior polar cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
early-onset sutural cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
total early-onset cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MIP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 12-56450109-G-T is Benign according to our data. Variant chr12-56450109-G-T is described in ClinVar as [Benign]. Clinvar id is 309866.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
MIP	NM_012064.4 link	c.*1171C>A	3_prime_UTR_variant	Exon 4 of 4	ENST00000652304.1	NP_036196.1	P30301
MIP	XM_011538354.2 link	c.*1171C>A	3_prime_UTR_variant	Exon 6 of 6		XP_011536656.1
MIP	XM_017019306.2 link	c.*1171C>A	3_prime_UTR_variant	Exon 4 of 4		XP_016874795.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ENSG00000285528	ENST00000648304.1 link	n.*1587C>A	non_coding_transcript_exon_variant	Exon 4 of 4		ENSP00000497190.1	A0A3B3IS89
MIP	ENST00000652304.1 link	c.*1171C>A	3_prime_UTR_variant	Exon 4 of 4	NM_012064.4	ENSP00000498622.1	P30301
ENSG00000285528	ENST00000648304.1 link	n.*1587C>A	3_prime_UTR_variant	Exon 4 of 4		ENSP00000497190.1	A0A3B3IS89

Frequencies

GnomAD3 genomes

AF:

0.376

AC:

56957

AN:

151496

Hom.:

11148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.313

Gnomad AMI

AF:

0.509

Gnomad AMR

AF:

0.307

Gnomad ASJ

AF:

0.324

Gnomad EAS

AF:

0.251

Gnomad SAS

AF:

0.433

Gnomad FIN

AF:

0.442

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.427

Gnomad OTH

AF:

0.327

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.376

AC:

57004

AN:

151612

Hom.:

11165

Cov.:

AF XY:

0.377

AC XY:

27912

AN XY:

74028

show subpopulations

African (AFR)

AF:

0.313

AC:

12945

AN:

41312

American (AMR)

AF:

0.306

AC:

4669

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.324

AC:

1126

AN:

3470

East Asian (EAS)

AF:

0.252

AC:

1304

AN:

5172

South Asian (SAS)

AF:

0.434

AC:

2091

AN:

4818

European-Finnish (FIN)

AF:

0.442

AC:

4595

AN:

10396

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.427

AC:

29025

AN:

67904

Other (OTH)

AF:

0.333

AC:

699

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1819

3638

5458

7277

9096

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.395

Hom.:

22480

Bravo

AF:

0.354

Asia WGS

AF:

0.371

AC:

1286

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cataract 15 multiple types

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.6

(source)

DANN

Benign

0.70

PhyloP100

-0.22

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

12-56450109-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over