chr12-56450041-C-CA

Variant names:

• chr12-56450041-C-CA
• rs111463603
• ENST00000648304.1:n.*1654dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000648304.1(ENSG00000285528):​n.*1654dupT variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.90 (60106 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000285528 ENST00000648304.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.669
• Publications: 1 publications found

Genes affected

ENSG00000285528 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIP	NM_012064.4	c.*1238dupT		3_prime_UTR_variant	Exon 4 of 4	ENST00000652304.1	NP_036196.1
MIP	XM_011538354.2	c.*1238dupT		3_prime_UTR_variant	Exon 6 of 6		XP_011536656.1
MIP	XM_017019306.2	c.*1238dupT		3_prime_UTR_variant	Exon 4 of 4		XP_016874795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285528	ENST00000648304.1	n.*1654dupT		non_coding_transcript_exon_variant	Exon 4 of 4			ENSP00000497190.1
MIP	ENST00000652304.1	c.*1238dupT		3_prime_UTR_variant	Exon 4 of 4		NM_012064.4	ENSP00000498622.1
ENSG00000285528	ENST00000648304.1	n.*1654dupT		3_prime_UTR_variant	Exon 4 of 4			ENSP00000497190.1

Frequencies

GnomAD3 genomes AF: 0.900 AC: 131927 AN: 146522 Hom.: 60101 Cov.: 0

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.994

Gnomad AMR AF: 0.948

Gnomad ASJ AF: 0.955

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.988

Gnomad FIN AF: 0.949

Gnomad MID AF: 0.955

Gnomad NFE AF: 0.968

Gnomad OTH AF: 0.926

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.900 AC: 131965 AN: 146596 Hom.: 60106 Cov.: 0 AF XY: 0.902 AC XY: 64159 AN XY: 71124

African (AFR) AF: 0.729 AC: 29146 AN: 39972

American (AMR) AF: 0.948 AC: 13958 AN: 14724

Ashkenazi Jewish (ASJ) AF: 0.955 AC: 3292 AN: 3446

East Asian (EAS) AF: 0.989 AC: 5022 AN: 5076

South Asian (SAS) AF: 0.988 AC: 4592 AN: 4648

European-Finnish (FIN) AF: 0.949 AC: 8428 AN: 8884

Middle Eastern (MID) AF: 0.951 AC: 270 AN: 284

European-Non Finnish (NFE) AF: 0.968 AC: 64476 AN: 66620

Other (OTH) AF: 0.923 AC: 1878 AN: 2034

Alfa AF: 0.928 Hom.: 2029

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cataract Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.67
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs111463603; hg19: chr12-56843825;