rs7953824

Variant names:

• chr12-56451574-T-C
• rs7953824
• NM_012064.4:c.607-109A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-56451574-T-C
• chr12-56451574-T-A
• chr12-56451574-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012064.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIP	NM_012064.4	MANE Select	c.607-109A>G		intron	N/A	NP_036196.1	P30301

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIP	ENST00000652304.1	MANE Select	c.607-109A>G		intron	N/A	ENSP00000498622.1	P30301
	ENSG00000285528	ENST00000648304.1		n.*231-109A>G		intron	N/A	ENSP00000497190.1	A0A3B3IS89
	MIP	ENST00000648442.1		n.740-109A>G		intron	N/A

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

African (AFR) AF: 0.155 AC: 2751 AN: 17696

American (AMR) AF: 0.547 AC: 16900 AN: 30874

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 8743 AN: 18288

East Asian (EAS) AF: 0.586 AC: 20985 AN: 35798

South Asian (SAS) AF: 0.407 AC: 25354 AN: 62226

European-Finnish (FIN) AF: 0.429 AC: 21282 AN: 49612

Middle Eastern (MID) AF: 0.484 AC: 1248 AN: 2576

European-Non Finnish (NFE) AF: 0.446 AC: 194365 AN: 435738

Other (OTH) AF: 0.449 AC: 15323 AN: 34156

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

African (AFR) AF: 0.161 AC: 6685 AN: 41520

American (AMR) AF: 0.471 AC: 7191 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1689 AN: 3464

East Asian (EAS) AF: 0.658 AC: 3408 AN: 5180

South Asian (SAS) AF: 0.403 AC: 1944 AN: 4818

European-Finnish (FIN) AF: 0.414 AC: 4380 AN: 10568

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30381 AN: 67962

Other (OTH) AF: 0.433 AC: 913 AN: 2108

Alfa AF: 0.315 Hom.: 1457

Bravo AF: 0.379

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.73
DANN	Benign	0.29
PhyloP100		2.0
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: rs7953824; hg19: chr12-56845358; COSMIC: COSV57509569; COSMIC: COSV57509569;