NM_001001683.4:c.*331A>G

Variant names:

• chr17-4733518-A-G
• rs1051007
• NM_001001683.4:c.*331A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001683.4. 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
	MED11	NM_001001683.4	MANE Select	c.*331A>G		3_prime_UTR	Exon 3 of 3	NP_001001683.1
	MED11	NM_001305000.2		c.*538A>G		3_prime_UTR	Exon 3 of 3	NP_001291929.1
	CXCL16	NM_001386809.1	MANE Select	c.*985T>C		downstream_gene	N/A	NP_001373738.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED11	ENST00000293777.6	TSL:1 MANE Select	c.*331A>G		3_prime_UTR	Exon 3 of 3	ENSP00000293777.5
	MED11	ENST00000674339.1		c.*446A>G		3_prime_UTR	Exon 2 of 2	ENSP00000501539.1
	CXCL16	ENST00000293778.12	TSL:1 MANE Select	c.*985T>C		downstream_gene	N/A	ENSP00000293778.7

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

African (AFR) AF: 0.105 AC: 305 AN: 2914

American (AMR) AF: 0.0789 AC: 273 AN: 3462

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 548 AN: 3060

East Asian (EAS) AF: 0.000532 AC: 3 AN: 5644

South Asian (SAS) AF: 0.0731 AC: 384 AN: 5256

European-Finnish (FIN) AF: 0.0813 AC: 349 AN: 4292

Middle Eastern (MID) AF: 0.137 AC: 55 AN: 402

European-Non Finnish (NFE) AF: 0.125 AC: 6552 AN: 52270

Other (OTH) AF: 0.117 AC: 635 AN: 5414

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

African (AFR) AF: 0.106 AC: 4407 AN: 41520

American (AMR) AF: 0.0986 AC: 1508 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 664 AN: 3470

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5186

South Asian (SAS) AF: 0.0646 AC: 312 AN: 4830

European-Finnish (FIN) AF: 0.0796 AC: 845 AN: 10612

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8548 AN: 68016

Other (OTH) AF: 0.130 AC: 275 AN: 2112

Alfa AF: 0.120 Hom.: 3410

Bravo AF: 0.113

Asia WGS AF: 0.0530 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.2
DANN	Benign	0.62
PhyloP100		0.20
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: rs1051007; hg19: chr17-4636813;