Genetic Variant MED15:p.Arg52fs (chr22-20537211-C-CCCTA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000263205.11(MED15):c.154_155insCCTA(p.Arg52fs) variant causes a frameshift, stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 1,611,884 control chromosomes in the GnomAD database, including 7,814 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.060 ( 648 hom., cov: 33)

Exomes 𝑓: 0.073 ( 7166 hom. )

Consequence

MED15
ENST00000263205.11 frameshift, stop_gained, splice_region

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.147

Variant links:

Genes affected

MED15 (HGNC:14248): (mediator complex subunit 15) The protein encoded by this gene is a subunit of the multiprotein complexes PC2 and ARC/DRIP and may function as a transcriptional coactivator in RNA polymerase II transcription. This gene contains stretches of trinucleotide repeats and is located in the chromosome 22 region which is deleted in DiGeorge syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

MED15 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 22-20537211-C-CCCTA is Benign according to our data. Variant chr22-20537211-C-CCCTA is described in ClinVar as [Benign]. Clinvar id is 770675.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED15	NM_001003891.3 link	c.156+8_156+11dupCCTA		intron_variant	Intron 2 of 17	ENST00000263205.11	NP_001003891.1	Q96RN5-1Q6PKB8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED15	ENST00000263205.11 link	c.154_155insCCTA	p.Arg52fs	frameshift_variant, stop_gained, splice_region_variant	Exon 2 of 18	1	NM_001003891.3	ENSP00000263205.7		Q96RN5-1

Frequencies

GnomAD3 genomes

AF:

0.0604

AC:

9190

AN:

152166

Hom.:

648

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0122

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0448

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.387

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.0711

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0580

Gnomad OTH

AF:

0.0675

GnomAD3 exomes

AF:

0.0934

AC:

23446

AN:

250970

Hom.:

2146

AF XY:

0.0972

AC XY:

13189

AN XY:

135640

show subpopulations

Gnomad AFR exome

AF:

0.0110

Gnomad AMR exome

AF:

0.0545

Gnomad ASJ exome

AF:

0.0958

Gnomad EAS exome

AF:

0.391

Gnomad SAS exome

AF:

0.152

Gnomad FIN exome

AF:

0.0709

Gnomad NFE exome

AF:

0.0582

Gnomad OTH exome

AF:

0.0773

GnomAD4 exome

AF:

0.0728

AC:

106319

AN:

1459602

Hom.:

7166

Cov.:

AF XY:

0.0762

AC XY:

55351

AN XY:

726268

show subpopulations

Gnomad4 AFR exome

AF:

0.00975

Gnomad4 AMR exome

AF:

0.0531

Gnomad4 ASJ exome

AF:

0.0984

Gnomad4 EAS exome

AF:

0.427

Gnomad4 SAS exome

AF:

0.157

Gnomad4 FIN exome

AF:

0.0671

Gnomad4 NFE exome

AF:

0.0554

Gnomad4 OTH exome

AF:

0.0797

GnomAD4 genome

AF:

0.0604

AC:

9191

AN:

152282

Hom.:

648

Cov.:

AF XY:

0.0642

AC XY:

4777

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0122

Gnomad4 AMR

AF:

0.0445

Gnomad4 ASJ

AF:

0.102

Gnomad4 EAS

AF:

0.387

Gnomad4 SAS

AF:

0.154

Gnomad4 FIN

AF:

0.0711

Gnomad4 NFE

AF:

0.0580

Gnomad4 OTH

AF:

0.0711

Alfa

AF:

0.0609

Hom.:

Bravo

AF:

0.0592

Asia WGS

AF:

0.242

AC:

840

AN:

3478

EpiCase

AF:

0.0597

EpiControl

AF:

0.0615

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 12, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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