22-20537211-C-CCCTA

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]

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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
MED15NM_001003891.3 linkc.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
MED15ENST00000263205.11 linkc.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.:
33
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.:
30
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.:
33
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.:
67
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.

Other links and lift over

dbSNP: rs148534902; hg19: chr22-20891498; API