rs7953824

Positions:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_012064.4(MIP):​c.607-109A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000305 in 840,462 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: MIP NM_012064.4 intron
• Clinical Significance: Not reported in ClinVar
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00116 (177/152146) while in subpopulation AFR AF= 0.00414 (172/41530). AF 95% confidence interval is 0.00364. There are 0 homozygotes in gnomad4. There are 95 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 177 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00113 AC: 172 AN: 152028 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00403

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000479

GnomAD4 exome AF: 0.000115 AC: 79 AN: 688316 Hom.: 0 AF XY: 0.0000826 AC XY: 30 AN XY: 363330

Gnomad4 AFR exome AF: 0.00378

Gnomad4 AMR exome AF: 0.000161

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000229

Gnomad4 OTH exome AF: 0.000175

GnomAD4 genome AF: 0.00116 AC: 177 AN: 152146 Hom.: 0 Cov.: 33 AF XY: 0.00128 AC XY: 95 AN XY: 74372

Gnomad4 AFR AF: 0.00414

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.61
DANN	Benign	0.23

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;