rs543401049

Variant names:

• chr6-14117976-G-A
• rs543401049
• NM_004233.4:c.64G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-14117976-G-A
• chr6-14117976-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004233.4(CD83):​c.64G>A​(p.Glu22Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,610,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CD83 NM_004233.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.09
• Publications: 1 publications found

Genes affected

CD83 (HGNC:1703): (CD83 molecule) The protein encoded by this gene is a single-pass type I membrane protein and member of the immunoglobulin superfamily of receptors. The encoded protein may be involved in the regulation of antigen presentation. A soluble form of this protein can bind to dendritic cells and inhibit their maturation. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20785704).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004233.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD83	NM_004233.4	MANE Select	c.64G>A	p.Glu22Lys	missense	Exon 2 of 5	NP_004224.1	Q01151
	CD83	NM_001040280.3		c.64G>A	p.Glu22Lys	missense	Exon 2 of 5	NP_001035370.1
	CD83	NM_001251901.1		c.-114G>A		5_prime_UTR	Exon 2 of 5	NP_001238830.1	A0A087WX61

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD83	ENST00000379153.4	TSL:1 MANE Select	c.64G>A	p.Glu22Lys	missense	Exon 2 of 5	ENSP00000368450.3	Q01151
	CD83	ENST00000857144.1		c.64G>A	p.Glu22Lys	missense	Exon 2 of 5	ENSP00000527203.1
	CD83	ENST00000925000.1		c.64G>A	p.Glu22Lys	missense	Exon 2 of 3	ENSP00000595059.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152134 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000406 AC: 1 AN: 246282 AF XY: 0.00000748

Gnomad AFR exome AF: 0.0000632

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458310 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725496

African (AFR) AF: 0.0000300 AC: 1 AN: 33336

American (AMR) AF: 0.00 AC: 0 AN: 44422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39498

South Asian (SAS) AF: 0.00 AC: 0 AN: 85854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51760

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111284

Other (OTH) AF: 0.00 AC: 0 AN: 60304

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152252 Hom.: 0 Cov.: 31 AF XY: 0.0000537 AC XY: 4 AN XY: 74446

African (AFR) AF: 0.000144 AC: 6 AN: 41568

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.71	D
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.1
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.065
Sift	Benign	0.061	T
Sift4G	Benign	0.15	T
Polyphen		0.77	P
Vest4		0.18
MutPred		0.71		Gain of ubiquitination at E22 (P = 0.0276)
MVP		0.16
MPC		0.31
ClinPred		0.25	T
GERP RS		0.89
PromoterAI		-0.029	Neutral
Varity_R		0.15
gMVP		0.53
Mutation Taster		=97/3	polymorphism

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: rs543401049; hg19: chr6-14118207;