rs1082214

Variant names:

• chr12-56452706-C-T
• rs1082214
• ENST00000555551.1:n.928G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000555551.1(MIP):​n.928G>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 0.0815 in 314,872 control chromosomes in the GnomAD database, including 1,323 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 0.093 (817 hom., cov: 32)
  • Exomes 𝑓: 0.071 (506 hom.)
• Consequence: MIP ENST00000555551.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131
• Publications: 16 publications found

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 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

ENSG00000285528 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIP	NM_012064.4	c.606+366G>A		intron_variant	Intron 3 of 3	ENST00000652304.1	NP_036196.1
MIP	XM_011538354.2	c.321+366G>A		intron_variant	Intron 5 of 5		XP_011536656.1
MIP	XM_017019306.2	c.249+366G>A		intron_variant	Intron 3 of 3		XP_016874795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIP	ENST00000652304.1	c.606+366G>A		intron_variant	Intron 3 of 3		NM_012064.4	ENSP00000498622.1
ENSG00000285528	ENST00000648304.1	n.*230+366G>A		intron_variant	Intron 3 of 3			ENSP00000497190.1

Frequencies

GnomAD3 genomes AF: 0.0930 AC: 14151 AN: 152084 Hom.: 817 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.0857

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0763

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0575

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.0707 AC: 11508 AN: 162670 Hom.: 506 Cov.: 0 AF XY: 0.0730 AC XY: 6351 AN XY: 86962

African (AFR) AF: 0.136 AC: 716 AN: 5264

American (AMR) AF: 0.137 AC: 980 AN: 7132

Ashkenazi Jewish (ASJ) AF: 0.0809 AC: 349 AN: 4314

East Asian (EAS) AF: 0.0787 AC: 643 AN: 8170

South Asian (SAS) AF: 0.0923 AC: 2499 AN: 27078

European-Finnish (FIN) AF: 0.0724 AC: 537 AN: 7422

Middle Eastern (MID) AF: 0.0949 AC: 59 AN: 622

European-Non Finnish (NFE) AF: 0.0548 AC: 5159 AN: 94204

Other (OTH) AF: 0.0669 AC: 566 AN: 8464

GnomAD4 genome AF: 0.0930 AC: 14160 AN: 152202 Hom.: 817 Cov.: 32 AF XY: 0.0962 AC XY: 7156 AN XY: 74410

African (AFR) AF: 0.142 AC: 5879 AN: 41522

American (AMR) AF: 0.132 AC: 2023 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0778 AC: 270 AN: 3472

East Asian (EAS) AF: 0.0849 AC: 440 AN: 5182

South Asian (SAS) AF: 0.105 AC: 506 AN: 4820

European-Finnish (FIN) AF: 0.0763 AC: 808 AN: 10590

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0575 AC: 3914 AN: 68012

Other (OTH) AF: 0.104 AC: 218 AN: 2104

Alfa AF: 0.0757 Hom.: 832

Bravo AF: 0.0991

Asia WGS AF: 0.114 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.33
DANN	Benign	0.58
PhyloP100		-0.13
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: rs1082214; hg19: chr12-56846490;