chr6-14135163-G-A

Position:

• chr6-14135163-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004233.4(CD83):​c.545G>A​(p.Arg182Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,613,782 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.014 (48 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (47 hom.)
• Consequence: CD83 NM_004233.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0540

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015002787).
• BP6: Variant 6-14135163-G-A is Benign according to our data. Variant chr6-14135163-G-A is described in ClinVar as [Benign]. Clinvar id is 782470.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0135 (2056/152264) while in subpopulation AFR AF= 0.0472 (1962/41542). AF 95% confidence interval is 0.0455. There are 48 homozygotes in gnomad4. There are 985 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD83	NM_004233.4	c.545G>A	p.Arg182Gln	missense_variant	5/5	ENST00000379153.4	NP_004224.1
CD83	NM_001040280.3	c.542G>A	p.Arg181Gln	missense_variant	5/5		NP_001035370.1
CD83	NM_001251901.1	c.368G>A	p.Arg123Gln	missense_variant	5/5		NP_001238830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD83	ENST00000379153.4	c.545G>A	p.Arg182Gln	missense_variant	5/5	1	NM_004233.4	ENSP00000368450.3
CD83	ENST00000612003.4	c.368G>A	p.Arg123Gln	missense_variant	5/5	4		ENSP00000480760.1

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 2058 AN: 152148 Hom.: 48 Cov.: 33

Gnomad AFR AF: 0.0474

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00355 AC: 892 AN: 251472 Hom.: 21 AF XY: 0.00261 AC XY: 355 AN XY: 135908

Gnomad AFR exome AF: 0.0482

Gnomad AMR exome AF: 0.00156

Gnomad ASJ exome AF: 0.00347

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.00134 AC: 1961 AN: 1461518 Hom.: 47 Cov.: 30 AF XY: 0.00111 AC XY: 804 AN XY: 727088

Gnomad4 AFR exome AF: 0.0475

Gnomad4 AMR exome AF: 0.00174

Gnomad4 ASJ exome AF: 0.00337

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000495

Gnomad4 OTH exome AF: 0.00235

GnomAD4 genome AF: 0.0135 AC: 2056 AN: 152264 Hom.: 48 Cov.: 33 AF XY: 0.0132 AC XY: 985 AN XY: 74454

Gnomad4 AFR AF: 0.0472

Gnomad4 AMR AF: 0.00392

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00239 Hom.: 7

Bravo AF: 0.0143

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0458 AC: 202

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.00441 AC: 536

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.91
DEOGEN2	Benign	0.028	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.74	T;T
MetaRNN	Benign	0.0015	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	.;L
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.85	.;N
REVEL	Benign	0.036
Sift	Benign	0.29	.;T
Sift4G	Benign	0.41	T;T
Polyphen		0.052	.;B
Vest4		0.022
MVP		0.081
MPC		0.30
ClinPred		0.0018	T
GERP RS		-4.0
Varity_R		0.031
gMVP		0.30

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: rs2230193; hg19: chr6-14135394;