Variant rs12552387 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The variant allele was found at a frequency of 0.000917 in 685,794 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00052 ( 3 hom. )

Consequence

intergenic_region

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -9.77

Variant links:

Genes affected

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 9-35658027-A-C is Benign according to our data. Variant chr9-35658027-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 533771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
	use as main transcript	n.35658027A>C		intergenic_region
RMRP	NR_003051.4 linkuse as main transcript	n.-8T>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RMRP	ENST00000363046.1 linkuse as main transcript	n.-10T>G		upstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.00230

AC:

350

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00639

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00360

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:

0.000294

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.000714

AC:

AN:

126116

Hom.:

AF XY:

0.000624

AC XY:

AN XY:

68902

show subpopulations

Gnomad AFR exome

AF:

0.00561

Gnomad AMR exome

AF:

0.00170

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000456

Gnomad FIN exome

AF:

0.000192

Gnomad NFE exome

AF:

0.000253

Gnomad OTH exome

AF:

0.000514

GnomAD4 exome

AF:

0.000521

AC:

278

AN:

533452

Hom.:

Cov.:

AF XY:

0.000495

AC XY:

142

AN XY:

286732

show subpopulations

Gnomad4 AFR exome

AF:

0.00553

Gnomad4 AMR exome

AF:

0.00192

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000645

Gnomad4 FIN exome

AF:

0.0000606

Gnomad4 NFE exome

AF:

0.000304

Gnomad4 OTH exome

AF:

0.000875

GnomAD4 genome

AF:

0.00230

AC:

351

AN:

152342

Hom.:

Cov.:

AF XY:

0.00221

AC XY:

165

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00640

Gnomad4 AMR

AF:

0.00359

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.000343

Hom.:

Bravo

AF:

0.00308

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Feb 18, 2022

Variant summary: RMRP n.-9T>G is located in the untranscribed region upstream of the RMRP gene region. The variant allele was found at a frequency of 0.00097 in 157506 control chromosomes in the gnomAD database, including 2 homozygotes. To our knowledge, no occurrence of n.-9T>G in individuals affected with Cartilage-Hair Hypoplasia and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign. -

Metaphyseal chondrodysplasia, McKusick type

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Natera, Inc.

Jul 27, 2020

- -

Anauxetic dysplasia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 14, 2022

Located in a region that tolerates variation and lacks pathogenic variants; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.0010

DANN

Benign

0.37

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