rs7047055

Variant names:

• chr9-131923979-T-C
• rs7047055
• NM_004269.4:c.573+15402A>G

Variant summary

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

The NM_004269.4(MED27):​c.573+15402A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,142 control chromosomes in the GnomAD database, including 15,660 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 0.44 (15660 hom., cov: 33)
• Consequence: MED27 NM_004269.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405
• Publications: 7 publications found

Genes affected

MED27 (HGNC:2377): (mediator complex subunit 27) The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 5. [provided by RefSeq, Dec 2011]

MED27 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia

  Inheritance: AR Classification: STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED27	NM_004269.4	c.573+15402A>G		intron_variant	Intron 4 of 7	ENST00000292035.10	NP_004260.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED27	ENST00000292035.10	c.573+15402A>G		intron_variant	Intron 4 of 7	1	NM_004269.4	ENSP00000292035.5
MED27	ENST00000357028.6	c.573+15402A>G		intron_variant	Intron 4 of 6	1		ENSP00000349530.3
MED27	ENST00000651950.1	c.573+15402A>G		intron_variant	Intron 4 of 8			ENSP00000498604.1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66336 AN: 152024 Hom.: 15655 Cov.: 33

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.461

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.436 AC: 66362 AN: 152142 Hom.: 15660 Cov.: 33 AF XY: 0.439 AC XY: 32620 AN XY: 74366

African (AFR) AF: 0.260 AC: 10803 AN: 41500

American (AMR) AF: 0.412 AC: 6293 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2042 AN: 3472

East Asian (EAS) AF: 0.285 AC: 1475 AN: 5180

South Asian (SAS) AF: 0.436 AC: 2100 AN: 4816

European-Finnish (FIN) AF: 0.604 AC: 6382 AN: 10570

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35713 AN: 68006

Other (OTH) AF: 0.462 AC: 975 AN: 2110

Alfa AF: 0.494 Hom.: 32923

Bravo AF: 0.412

Asia WGS AF: 0.369 AC: 1289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.39
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7047055; hg19: chr9-134799366;