12-56451574-T-C

Position:

• chr12-56451574-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012064.4(MIP):​c.607-109A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 839,064 control chromosomes in the GnomAD database, including 82,534 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (12331 hom., cov: 33)
  • Exomes 𝑓: 0.45 (70203 hom.)
• Consequence: MIP NM_012064.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.02

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]

ENSG00000285528 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 12-56451574-T-C is Benign according to our data. Variant chr12-56451574-T-C is described in ClinVar as [Benign]. Clinvar id is 1237455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIP	NM_012064.4	c.607-109A>G		intron_variant		ENST00000652304.1	NP_036196.1
MIP	XM_011538354.2	c.322-109A>G		intron_variant			XP_011536656.1
MIP	XM_017019306.2	c.250-109A>G		intron_variant			XP_016874795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIP	ENST00000652304.1	c.607-109A>G		intron_variant			NM_012064.4	ENSP00000498622.1
ENSG00000285528	ENST00000648304.1	n.*231-109A>G		intron_variant				ENSP00000497190.1
MIP	ENST00000648442.1	n.740-109A>G		intron_variant
MIP	ENST00000650166.1	n.496-109A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.375 AC: 57042 AN: 151982 Hom.: 12332 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.658

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.438

GnomAD4 exome AF: 0.447 AC: 306951 AN: 686964 Hom.: 70203 AF XY: 0.445 AC XY: 161525 AN XY: 362670

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.547

Gnomad4 ASJ exome AF: 0.478

Gnomad4 EAS exome AF: 0.586

Gnomad4 SAS exome AF: 0.407

Gnomad4 FIN exome AF: 0.429

Gnomad4 NFE exome AF: 0.446

Gnomad4 OTH exome AF: 0.449

GnomAD4 genome AF: 0.375 AC: 57029 AN: 152100 Hom.: 12331 Cov.: 33 AF XY: 0.377 AC XY: 28062 AN XY: 74340

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.471

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.433

Alfa AF: 0.320 Hom.: 1446

Bravo AF: 0.379

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.73
DANN	Benign	0.29

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: rs7953824; hg19: chr12-56845358; COSMIC: COSV57509569; COSMIC: COSV57509569;