rs1242502

Positions:

• chr17-17478450-T-C
• chr17-17478450-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018019.3(MED9):​c.224+1185T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 152,120 control chromosomes in the GnomAD database, including 36,004 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 0.68 (36004 hom., cov: 33)
• Consequence: MED9 NM_018019.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154

Genes affected

MED9 (HGNC:25487): (mediator complex subunit 9) The multiprotein Mediator complex is a coactivator required for activation of RNA polymerase II transcription by DNA bound transcription factors. The protein encoded by this gene is thought to be a subunit of the Mediator complex. This gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MED9	NM_018019.3	c.224+1185T>C		intron_variant		ENST00000268711.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED9	ENST00000268711.4	c.224+1185T>C		intron_variant		1	NM_018019.3	P1
MED9	ENST00000580462.1	c.224+1185T>C		intron_variant		1
MED9	ENST00000581315.1	c.224+1185T>C		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103530 AN: 152004 Hom.: 35986 Cov.: 33

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.680

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

GnomAD4 genome AF: 0.681 AC: 103608 AN: 152120 Hom.: 36004 Cov.: 33 AF XY: 0.674 AC XY: 50134 AN XY: 74368

Gnomad4 AFR AF: 0.639

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.699

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.676

Alfa AF: 0.725 Hom.: 19571

Bravo AF: 0.672

Asia WGS AF: 0.448 AC: 1560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.6
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs1242502; hg19: chr17-17381764; COSMIC: COSV51957049; COSMIC: COSV51957049;