rs774053

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000648304.1(ENSG00000285528):n.*921T>C 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 0.85 in 163,274 control chromosomes in the GnomAD database, including 60,703 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.84 ( 55678 hom., cov: 30)

Exomes 𝑓: 0.94 ( 5025 hom. )

Consequence

ENSG00000285528
ENST00000648304.1 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.466

Publications

6 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MIP	NM_012064.4 link	c.*505T>C	3_prime_UTR_variant	Exon 4 of 4	ENST00000652304.1	NP_036196.1	P30301
MIP	XM_011538354.2 link	c.*505T>C	3_prime_UTR_variant	Exon 6 of 6		XP_011536656.1
MIP	XM_017019306.2 link	c.*505T>C	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.*921T>C	non_coding_transcript_exon_variant	Exon 4 of 4		ENSP00000497190.1	A0A3B3IS89
MIP	ENST00000652304.1 link	c.*505T>C	3_prime_UTR_variant	Exon 4 of 4	NM_012064.4	ENSP00000498622.1	P30301
ENSG00000285528	ENST00000648304.1 link	n.*921T>C	3_prime_UTR_variant	Exon 4 of 4		ENSP00000497190.1	A0A3B3IS89

Frequencies

GnomAD3 genomes

AF:

0.844

AC:

128104

AN:

151834

Hom.:

55666

Cov.:

show subpopulations

Gnomad AFR

AF:

0.608

Gnomad AMI

AF:

0.934

Gnomad AMR

AF:

0.913

Gnomad ASJ

AF:

0.889

Gnomad EAS

AF:

0.995

Gnomad SAS

AF:

0.954

Gnomad FIN

AF:

0.934

Gnomad MID

AF:

0.832

Gnomad NFE

AF:

0.933

Gnomad OTH

AF:

0.868

GnomAD4 exome

AF:

0.941

AC:

10653

AN:

11322

Hom.:

5025

Cov.:

AF XY:

0.943

AC XY:

5822

AN XY:

6172

show subpopulations

African (AFR)

AF:

0.482

AC:

AN:

American (AMR)

AF:

0.933

AC:

1840

AN:

1972

Ashkenazi Jewish (ASJ)

AF:

0.823

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

362

AN:

362

South Asian (SAS)

AF:

0.961

AC:

1540

AN:

1602

European-Finnish (FIN)

AF:

0.932

AC:

505

AN:

542

Middle Eastern (MID)

AF:

0.833

AC:

AN:

European-Non Finnish (NFE)

AF:

0.944

AC:

5880

AN:

6232

Other (OTH)

AF:

0.915

AC:

410

AN:

448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

114

143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.843

AC:

128156

AN:

151952

Hom.:

55678

Cov.:

AF XY:

0.850

AC XY:

63113

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.608

AC:

25125

AN:

41330

American (AMR)

AF:

0.913

AC:

13937

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.889

AC:

3085

AN:

3470

East Asian (EAS)

AF:

0.995

AC:

5147

AN:

5174

South Asian (SAS)

AF:

0.955

AC:

4597

AN:

4816

European-Finnish (FIN)

AF:

0.934

AC:

9880

AN:

10578

Middle Eastern (MID)

AF:

0.837

AC:

246

AN:

294

European-Non Finnish (NFE)

AF:

0.933

AC:

63460

AN:

68004

Other (OTH)

AF:

0.867

AC:

1829

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

878

1756

2635

3513

4391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.874

Hom.:

23876

Bravo

AF:

0.832

Asia WGS

AF:

0.944

AC:

3282

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.9

(source)

DANN

Benign

0.76

PhyloP100

0.47

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.

rs774053

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over