14-70594120-A-G

Variant names:

• chr14-70594120-A-G
• rs10483832
• NM_005466.4:c.275-742T>C

Variant summary

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

The NM_005466.4(MED6):​c.275-742T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,126 control chromosomes in the GnomAD database, including 3,399 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 0.18 (3399 hom., cov: 32)
• Consequence: MED6 NM_005466.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.307
• Publications: 9 publications found

Genes affected

MED6 (HGNC:19970): (mediator complex subunit 6) Enables transcription coactivator activity. Acts upstream of or within positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of mediator complex. [provided by Alliance of Genome Resources, Apr 2022]

DUXAP12 (HGNC:51813):

ENSG00000259115 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED6	NM_005466.4	c.275-742T>C		intron_variant	Intron 3 of 7	ENST00000256379.10	NP_005457.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED6	ENST00000256379.10	c.275-742T>C		intron_variant	Intron 3 of 7	1	NM_005466.4	ENSP00000256379.5

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28031 AN: 152008 Hom.: 3381 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.0830

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.185 AC: 28094 AN: 152126 Hom.: 3399 Cov.: 32 AF XY: 0.185 AC XY: 13758 AN XY: 74396

African (AFR) AF: 0.294 AC: 12187 AN: 41444

American (AMR) AF: 0.142 AC: 2171 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 490 AN: 3466

East Asian (EAS) AF: 0.523 AC: 2706 AN: 5170

South Asian (SAS) AF: 0.173 AC: 835 AN: 4824

European-Finnish (FIN) AF: 0.0830 AC: 881 AN: 10610

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8236 AN: 68008

Other (OTH) AF: 0.199 AC: 420 AN: 2112

Alfa AF: 0.144 Hom.: 6169

Bravo AF: 0.197

Asia WGS AF: 0.389 AC: 1352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.69
PhyloP100		0.31
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: rs10483832; hg19: chr14-71060837;