rs148534902

Variant names:

• chr22-20537211-C-CCCTA
• rs148534902
• ENST00000263205.11:c.154_155insCCTA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.147
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000263205.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED15	NM_001003891.3	MANE Select	c.156+8_156+11dupCCTA		intron	N/A	NP_001003891.1	Q96RN5-1
	MED15	NM_015889.5		c.156+8_156+11dupCCTA		intron	N/A	NP_056973.2
	MED15	NM_001293234.2		c.156+8_156+11dupCCTA		intron	N/A	NP_001280163.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED15	ENST00000263205.11	TSL:1 MANE Select	c.154_155insCCTA	p.Arg52fs	frameshift stop_gained splice_region	Exon 2 of 18	ENSP00000263205.7	Q96RN5-1
	MED15	ENST00000292733.11	TSL:1	c.154_155insCCTA	p.Arg52fs	frameshift stop_gained splice_region	Exon 2 of 17	ENSP00000292733.7	Q96RN5-2
	MED15	ENST00000406969.5	TSL:1	c.76_77insCCTA	p.Arg26fs	frameshift stop_gained splice_region	Exon 2 of 17	ENSP00000384344.1	G3V1P5

Frequencies

GnomAD3 genomes AF: 0.0604 AC: 9190 AN: 152166 Hom.: 648 Cov.: 33

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

GnomAD2 exomes AF: 0.0934 AC: 23446 AN: 250970 AF XY: 0.0972

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 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

African (AFR) AF: 0.00975 AC: 326 AN: 33438

American (AMR) AF: 0.0531 AC: 2371 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.0984 AC: 2567 AN: 26088

East Asian (EAS) AF: 0.427 AC: 16912 AN: 39610

South Asian (SAS) AF: 0.157 AC: 13562 AN: 86158

European-Finnish (FIN) AF: 0.0671 AC: 3573 AN: 53248

Middle Eastern (MID) AF: 0.115 AC: 661 AN: 5754

European-Non Finnish (NFE) AF: 0.0554 AC: 61542 AN: 1110320

Other (OTH) AF: 0.0797 AC: 4805 AN: 60304

GnomAD4 genome AF: 0.0604 AC: 9191 AN: 152282 Hom.: 648 Cov.: 33 AF XY: 0.0642 AC XY: 4777 AN XY: 74456

African (AFR) AF: 0.0122 AC: 507 AN: 41584

American (AMR) AF: 0.0445 AC: 681 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 354 AN: 3470

East Asian (EAS) AF: 0.387 AC: 1996 AN: 5160

South Asian (SAS) AF: 0.154 AC: 745 AN: 4824

European-Finnish (FIN) AF: 0.0711 AC: 754 AN: 10612

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0580 AC: 3948 AN: 68022

Other (OTH) AF: 0.0711 AC: 150 AN: 2110

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.15
Mutation Taster		=78/22	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs148534902; hg19: chr22-20891498;