chr12-56450109-G-T

Position:

• chr12-56450109-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012064.4(MIP):​c.*1171C>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 0.376 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: MIP NM_012064.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.219

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]

ACMG classification

Verdict is Benign. Variant got -14 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_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	HGVSp	Effect	#exon/exons	MANE	UniProt
MIP	NM_012064.4	c.*1171C>A		3_prime_UTR_variant	4/4	ENST00000652304.1
MIP	XM_011538354.2	c.*1171C>A		3_prime_UTR_variant	6/6
MIP	XM_017019306.2	c.*1171C>A		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIP	ENST00000652304.1	c.*1171C>A		3_prime_UTR_variant	4/4		NM_012064.4	P1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 56957 AN: 151496 Hom.: 11148 Cov.: 31

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: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.376 AC: 57004 AN: 151612 Hom.: 11165 Cov.: 31 AF XY: 0.377 AC XY: 27912 AN XY: 74028

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.333

Alfa AF: 0.400 Hom.: 16850

Bravo AF: 0.354

Asia WGS AF: 0.371 AC: 1286 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	-0.82
CADD	Benign	7.6
DANN	Benign	0.70

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

Other links and lift over

dbSNP: rs2371455; hg19: chr12-56843893;