chr8-117537137-T-C

Variant names:

• chr8-117537137-T-C
• rs17667932
• NM_080651.4:c.442-2746T>C

Variant summary

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

The NM_080651.4(MED30):​c.442-2746T>C variant causes a intron 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_080651.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.997
• Publications: 9 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080651.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED30	NM_080651.4	MANE Select	c.442-2746T>C		intron	N/A	NP_542382.1
	MED30	NM_001363182.2		c.*1004T>C		3_prime_UTR	Exon 4 of 4	NP_001350111.1
	MED30	NM_001282986.2		c.337-2746T>C		intron	N/A	NP_001269915.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED30	ENST00000297347.7	TSL:1 MANE Select	c.442-2746T>C		intron	N/A	ENSP00000297347.3
	MED30	ENST00000522839.1	TSL:1	c.337-2746T>C		intron	N/A	ENSP00000431051.1
	MED30	ENST00000519391.1	TSL:2	n.465-2746T>C		intron	N/A

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

African (AFR) AF: 0.0614 AC: 2553 AN: 41584

American (AMR) AF: 0.0720 AC: 1102 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 453 AN: 3470

East Asian (EAS) AF: 0.0409 AC: 212 AN: 5188

South Asian (SAS) AF: 0.124 AC: 600 AN: 4830

European-Finnish (FIN) AF: 0.123 AC: 1302 AN: 10602

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0731 AC: 4976 AN: 68028

Other (OTH) AF: 0.0757 AC: 160 AN: 2114

Alfa AF: 0.0726 Hom.: 1291

Bravo AF: 0.0683

Asia WGS AF: 0.0890 AC: 310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.87
PhyloP100		1.0
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: rs17667932; hg19: chr8-118549376;