chr14-70587761-T-C

Variant names:

• chr14-70587761-T-C
• rs10483830
• NM_005466.4:c.583-1978A>G

Variant summary

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

The NM_005466.4(MED6):​c.583-1978A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,228 control chromosomes in the GnomAD database, including 1,455 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 0.11 (1455 hom., cov: 32)
• Consequence: MED6 NM_005466.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 1 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED6	NM_005466.4	c.583-1978A>G		intron_variant	Intron 6 of 7	ENST00000256379.10	NP_005457.2
MED6	NM_001284211.2	c.583-1978A>G		intron_variant	Intron 6 of 8		NP_001271140.1
MED6	NM_001284209.2	c.604-1978A>G		intron_variant	Intron 6 of 7		NP_001271138.1
MED6	NM_001284210.2	c.467-1978A>G		intron_variant	Intron 5 of 6		NP_001271139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED6	ENST00000256379.10	c.583-1978A>G		intron_variant	Intron 6 of 7	1	NM_005466.4	ENSP00000256379.5

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17485 AN: 152110 Hom.: 1456 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0885

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0862

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.115 AC: 17498 AN: 152228 Hom.: 1455 Cov.: 32 AF XY: 0.116 AC XY: 8663 AN XY: 74434

African (AFR) AF: 0.131 AC: 5430 AN: 41538

American (AMR) AF: 0.102 AC: 1555 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0885 AC: 307 AN: 3468

East Asian (EAS) AF: 0.486 AC: 2510 AN: 5166

South Asian (SAS) AF: 0.151 AC: 730 AN: 4826

European-Finnish (FIN) AF: 0.0648 AC: 688 AN: 10618

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0862 AC: 5864 AN: 67990

Other (OTH) AF: 0.135 AC: 286 AN: 2114

Alfa AF: 0.0936 Hom.: 90

Bravo AF: 0.122

Asia WGS AF: 0.336 AC: 1165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.0
DANN	Benign	0.74
PhyloP100		-1.1
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: rs10483830; hg19: chr14-71054478;