rs1051007

chr17-4733518-A-G

Variant summary

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

The NM_001001683.4(MED11):c.*331A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 234,964 control chromosomes in the GnomAD database, including 1,601 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 (986 hom., cov: 32)
  • Exomes 𝑓: 0.11 (615 hom.)
• Consequence: MED11 NM_001001683.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198

Genes affected

MED11 (HGNC:32687): (mediator complex subunit 11) MED11 is a component of the Mediator complex, which is a coactivator for DNA-binding factors that activate transcription via RNA polymerase II (Sato et al., 2003 [PubMed 12584197]).[supplied by OMIM, Oct 2008]

CXCL16 (HGNC:16642): (C-X-C motif chemokine ligand 16) Enables chemokine activity. Involved in several processes, including positive regulation of cell growth; response to interferon-gamma; and response to tumor necrosis factor. Located in extracellular space. Biomarker of COVID-19 and systemic scleroderma. [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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MED11	NM_001001683.4	c.*331A>G		3_prime_UTR_variant	3/3	ENST00000293777.6
MED11	NM_001305000.2	c.*538A>G		3_prime_UTR_variant	3/3
CXCL16	NM_001386809.1			downstream_gene_variant		ENST00000293778.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED11	ENST00000293777.6	c.*331A>G		3_prime_UTR_variant	3/3	1	NM_001001683.4	P1
MED11	ENST00000674339.1	c.*446A>G		3_prime_UTR_variant	2/2
CXCL16	ENST00000293778.12			downstream_gene_variant		1	NM_001386809.1	P1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16746 AN: 152132 Hom.: 984 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.0987

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0639

Gnomad FIN AF: 0.0796

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.110 AC: 9104 AN: 82714 Hom.: 615 Cov.: 0 AF XY: 0.109 AC XY: 4642 AN XY: 42530

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.0789

Gnomad4 ASJ exome AF: 0.179

Gnomad4 EAS exome AF: 0.000532

Gnomad4 SAS exome AF: 0.0731

Gnomad4 FIN exome AF: 0.0813

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.110 AC: 16762 AN: 152250 Hom.: 986 Cov.: 32 AF XY: 0.106 AC XY: 7879 AN XY: 74442

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.0986

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0646

Gnomad4 FIN AF: 0.0796

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.130

Alfa AF: 0.123 Hom.: 1562

Bravo AF: 0.113

Asia WGS AF: 0.0530 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.2
Dann	Benign	0.62

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: rs1051007; hg19: chr17-4636813;