chr12-56452706-C-T

Position:

• chr12-56452706-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012064.4(MIP):​c.606+366G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0815 in 314,872 control chromosomes in the GnomAD database, including 1,323 homozygotes. 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 0.093 (817 hom., cov: 32)
  • Exomes 𝑓: 0.071 (506 hom.)
• Consequence: MIP NM_012064.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIP	NM_012064.4	c.606+366G>A		intron_variant		ENST00000652304.1	NP_036196.1
MIP	XM_011538354.2	c.321+366G>A		intron_variant			XP_011536656.1
MIP	XM_017019306.2	c.249+366G>A		intron_variant			XP_016874795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIP	ENST00000652304.1	c.606+366G>A		intron_variant			NM_012064.4	ENSP00000498622	P1
MIP	ENST00000555551.1	n.928G>A		non_coding_transcript_exon_variant	3/3	1
MIP	ENST00000648442.1	n.739+366G>A		intron_variant, non_coding_transcript_variant
MIP	ENST00000650166.1	n.495+366G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0930 AC: 14151 AN: 152084 Hom.: 817 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.0857

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0763

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0575

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.0707 AC: 11508 AN: 162670 Hom.: 506 Cov.: 0 AF XY: 0.0730 AC XY: 6351 AN XY: 86962

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.0809

Gnomad4 EAS exome AF: 0.0787

Gnomad4 SAS exome AF: 0.0923

Gnomad4 FIN exome AF: 0.0724

Gnomad4 NFE exome AF: 0.0548

Gnomad4 OTH exome AF: 0.0669

GnomAD4 genome AF: 0.0930 AC: 14160 AN: 152202 Hom.: 817 Cov.: 32 AF XY: 0.0962 AC XY: 7156 AN XY: 74410

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.0778

Gnomad4 EAS AF: 0.0849

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0763

Gnomad4 NFE AF: 0.0575

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0716 Hom.: 512

Bravo AF: 0.0991

Asia WGS AF: 0.114 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.33
DANN	Benign	0.58

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: rs1082214; hg19: chr12-56846490;