NM_004233.4:c.489+97T>A

Variant names:

• chr6-14133852-T-A
• rs9296925
• NM_004233.4:c.489+97T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004233.4(CD83):​c.489+97T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000164 in 608,780 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CD83 NM_004233.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.10
• Publications: 10 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD83	NM_004233.4	c.489+97T>A		intron_variant	Intron 4 of 4	ENST00000379153.4	NP_004224.1
CD83	NM_001040280.3	c.489+97T>A		intron_variant	Intron 4 of 4		NP_001035370.1
CD83	NM_001251901.1	c.312+97T>A		intron_variant	Intron 4 of 4		NP_001238830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD83	ENST00000379153.4	c.489+97T>A		intron_variant	Intron 4 of 4	1	NM_004233.4	ENSP00000368450.3
CD83	ENST00000612003.5	c.312+97T>A		intron_variant	Intron 4 of 4	4		ENSP00000480760.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 150354 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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

GnomAD4 exome AF: 0.00000164 AC: 1 AN: 608780 Hom.: 0 AF XY: 0.00000314 AC XY: 1 AN XY: 318182

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 14528

American (AMR) AF: 0.00 AC: 0 AN: 25802

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16276

East Asian (EAS) AF: 0.00 AC: 0 AN: 32458

South Asian (SAS) AF: 0.00 AC: 0 AN: 50434

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3138

European-Non Finnish (NFE) AF: 0.00000253 AC: 1 AN: 395984

Other (OTH) AF: 0.00 AC: 0 AN: 30688

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 150354 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73420

African (AFR) AF: 0.00 AC: 0 AN: 39836

American (AMR) AF: 0.00 AC: 0 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67962

Other (OTH) AF: 0.00 AC: 0 AN: 2068

Alfa AF: 0.00 Hom.: 23504

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.042
DANN	Benign	0.24
PhyloP100		-4.1

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: rs9296925; hg19: chr6-14134083;