chr12-27046247-G-A

Variant names:

• chr12-27046247-G-A
• rs1388659
• ENST00000538186.5:n.225+15G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000538186.5(MED21):​n.225+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,036 control chromosomes in the GnomAD database, including 10,131 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 0.34 (10130 hom., cov: 32)
  • Exomes 𝑓: 0.30 (1 hom.)
• Consequence: MED21 ENST00000538186.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• Publications: 11 publications found

Genes affected

MED21 (HGNC:11473): (mediator complex subunit 21) This gene encodes a member of the mediator complex subunit 21 family. The encoded protein interacts with the human RNA polymerase II holoenzyme and is involved in transcriptional regulation of RNA polymerase II transcribed genes. A pseudogene of this gene is located on chromosome 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED21	ENST00000538186.5	n.225+15G>A		intron_variant	Intron 3 of 4	3
MED21	ENST00000544998.1	n.81+15G>A		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51358 AN: 151908 Hom.: 10126 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.0325

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.336

GnomAD4 exome AF: 0.300 AC: 3 AN: 10 Hom.: 1 Cov.: 0 AF XY: 0.300 AC XY: 3 AN XY: 10

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.375 AC: 3 AN: 8

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.338 AC: 51384 AN: 152026 Hom.: 10130 Cov.: 32 AF XY: 0.333 AC XY: 24711 AN XY: 74290

African (AFR) AF: 0.178 AC: 7384 AN: 41482

American (AMR) AF: 0.266 AC: 4061 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1200 AN: 3466

East Asian (EAS) AF: 0.0326 AC: 169 AN: 5186

South Asian (SAS) AF: 0.224 AC: 1080 AN: 4830

European-Finnish (FIN) AF: 0.448 AC: 4730 AN: 10566

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.466 AC: 31651 AN: 67932

Other (OTH) AF: 0.334 AC: 706 AN: 2114

Alfa AF: 0.417 Hom.: 57829

Bravo AF: 0.317

Asia WGS AF: 0.144 AC: 502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.12
PhyloP100		0.062

Splicing

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

Other links and lift over

dbSNP: rs1388659; hg19: chr12-27199180;