Variant 12-56454697-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000648304.1(ENSG00000285528):n.183-942A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,576,206 control chromosomes in the GnomAD database, including 151,506 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 12330 hom., cov: 31)

Exomes 𝑓: 0.44 ( 139176 hom. )

Consequence

ENSG00000285528
ENST00000648304.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0510

Variant links:

Genes affected

MIP (HGNC:):

MIP 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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 12-56454697-T-C is Benign according to our data. Variant chr12-56454697-T-C is described in ClinVar as [Benign]. Clinvar id is 1231706.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	XM_011538354.2 linkuse as main transcript	c.76-942A>G		intron_variant			XP_011536656.1
MIP	NM_012064.4 linkuse as main transcript	c.-84A>G		upstream_gene_variant		ENST00000652304.1	NP_036196.1	P30301

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000285528	ENST00000648304.1 linkuse as main transcript	n.183-942A>G		intron_variant				ENSP00000497190.1		A0A3B3IS89
MIP	ENST00000652304.1 linkuse as main transcript	c.-84A>G		upstream_gene_variant			NM_012064.4	ENSP00000498622.1		P30301

Frequencies

GnomAD3 genomes

AF:

0.375

AC:

57001

AN:

151930

Hom.:

12331

Cov.:

show subpopulations

Gnomad AFR

AF:

0.162

Gnomad AMI

AF:

0.345

Gnomad AMR

AF:

0.470

Gnomad ASJ

AF:

0.487

Gnomad EAS

AF:

0.658

Gnomad SAS

AF:

0.402

Gnomad FIN

AF:

0.413

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.447

Gnomad OTH

AF:

0.435

GnomAD4 exome

AF:

0.438

AC:

623425

AN:

1424158

Hom.:

139176

AF XY:

0.437

AC XY:

309857

AN XY:

708330

show subpopulations

Gnomad4 AFR exome

AF:

0.150

Gnomad4 AMR exome

AF:

0.568

Gnomad4 ASJ exome

AF:

0.482

Gnomad4 EAS exome

AF:

0.594

Gnomad4 SAS exome

AF:

0.409

Gnomad4 FIN exome

AF:

0.428

Gnomad4 NFE exome

AF:

0.437

Gnomad4 OTH exome

AF:

0.440

GnomAD4 genome

AF:

0.375

AC:

56988

AN:

152048

Hom.:

12330

Cov.:

AF XY:

0.377

AC XY:

28030

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.161

Gnomad4 AMR

AF:

0.470

Gnomad4 ASJ

AF:

0.487

Gnomad4 EAS

AF:

0.658

Gnomad4 SAS

AF:

0.403

Gnomad4 FIN

AF:

0.413

Gnomad4 NFE

AF:

0.447

Gnomad4 OTH

AF:

0.431

Alfa

AF:

0.423

Hom.:

1786

Bravo

AF:

0.379

Asia WGS

AF:

0.441

AC:

1538

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.83

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over