rs973328

Positions:

• chr12-68294126-C-G
• chr12-68294126-C-T

Variant summary

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

The variant allele was found at a frequency of 0.306 in 152,054 control chromosomes in the GnomAD database, including 8,321 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 0.31 (8321 hom., cov: 33)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.463

Genes affected

(HGNC:):

MDM1 (HGNC:29917): (Mdm1 nuclear protein) This gene encodes a microtubule-binding nuclear protein that localizes to the centrioles of dividing cells and differentiating multiciliated cells and negatively regulates centriole duplication. The encoded protein is closely associated with the centriole barrel, and resides in the centriole lumen. Naturally-occurring mutations in the orthologous mouse gene are associated with age-related retinal degeneration. [provided by RefSeq, Feb 2019]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.68294126C>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MDM1	ENST00000357874.3	n.57+1139G>C		intron_variant		5		ENSP00000350544.3

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46573 AN: 151936 Hom.: 8319 Cov.: 33

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.301

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.306 AC: 46588 AN: 152054 Hom.: 8321 Cov.: 33 AF XY: 0.314 AC XY: 23322 AN XY: 74314

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.298

Alfa AF: 0.215 Hom.: 549

Bravo AF: 0.290

Asia WGS AF: 0.192 AC: 665 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs973328; hg19: chr12-68687906;