14-70587761-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MED6	NM_005466.4	c.583-1978A>G		intron_variant		ENST00000256379.10
MED6	NM_001284209.2	c.604-1978A>G		intron_variant
MED6	NM_001284210.2	c.467-1978A>G		intron_variant
MED6	NM_001284211.2	c.583-1978A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED6	ENST00000256379.10	c.583-1978A>G		intron_variant		1	NM_005466.4	P4

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

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0885

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.0648

Gnomad4 NFE AF: 0.0862

Gnomad4 OTH AF: 0.135

Alfa AF: 0.0929 Hom.: 84

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

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: rs10483830; hg19: chr14-71054478;