rs17667932

Positions:

• chr8-117537137-T-C

Variant summary

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

The NM_001363182.2(MED30):​c.*1004T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0753 in 152,328 control chromosomes in the GnomAD database, including 508 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 0.075 (508 hom., cov: 33)
• Consequence: MED30 NM_001363182.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.997

Genes affected

MED30 (HGNC:23032): (mediator complex subunit 30) The multiprotein TRAP/Mediator complex facilitates gene expression through a wide variety of transcriptional activators. MED30 is a component of this complex that appears to be metazoan specific (Baek et al., 2002 [PubMed 11909976]).[supplied by OMIM, Nov 2010]

MED30 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED30	NM_080651.4	c.442-2746T>C		intron_variant		ENST00000297347.7	NP_542382.1
MED30	NM_001363182.2	c.*1004T>C		3_prime_UTR_variant	4/4		NP_001350111.1
MED30	NM_001282986.2	c.337-2746T>C		intron_variant			NP_001269915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED30	ENST00000297347.7	c.442-2746T>C		intron_variant		1	NM_080651.4	ENSP00000297347.3
MED30	ENST00000522839.1	c.337-2746T>C		intron_variant		1		ENSP00000431051.1
MED30	ENST00000519391.1	n.465-2746T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0752 AC: 11453 AN: 152210 Hom.: 508 Cov.: 33

Gnomad AFR AF: 0.0614

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0721

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0408

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0731

Gnomad OTH AF: 0.0765

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

GnomAD4 genome AF: 0.0753 AC: 11463 AN: 152328 Hom.: 508 Cov.: 33 AF XY: 0.0782 AC XY: 5821 AN XY: 74480

Gnomad4 AFR AF: 0.0614

Gnomad4 AMR AF: 0.0720

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.0409

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.0731

Gnomad4 OTH AF: 0.0757

Alfa AF: 0.0725 Hom.: 464

Bravo AF: 0.0683

Asia WGS AF: 0.0890 AC: 310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.87

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: rs17667932; hg19: chr8-118549376;