rs6853

Positions:

• chr3-38142879-A-G
• chr3-38142879-A-T

Variant summary

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

The NM_002468.5(MYD88):​c.*1593A>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 0.142 in 233,104 control chromosomes in the GnomAD database, including 2,853 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 0.15 (2150 hom., cov: 32)
  • Exomes 𝑓: 0.12 (703 hom.)
• Consequence: MYD88 NM_002468.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287

Genes affected

MYD88 (HGNC:7562): (MYD88 innate immune signal transduction adaptor) This gene encodes a cytosolic adapter protein that plays a central role in the innate and adaptive immune response. This protein functions as an essential signal transducer in the interleukin-1 and Toll-like receptor signaling pathways. These pathways regulate that activation of numerous proinflammatory genes. The encoded protein consists of an N-terminal death domain and a C-terminal Toll-interleukin1 receptor domain. Patients with defects in this gene have an increased susceptibility to pyogenic bacterial infections. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

MYD88 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYD88	NM_002468.5	c.*1593A>G		3_prime_UTR_variant	5/5	ENST00000650905.2	NP_002459.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYD88	ENST00000650905.2	c.*1593A>G		3_prime_UTR_variant	5/5		NM_002468.5	ENSP00000498360.2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23489 AN: 152038 Hom.: 2141 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0257

Gnomad SAS AF: 0.0691

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.119 AC: 9663 AN: 80948 Hom.: 703 Cov.: 0 AF XY: 0.120 AC XY: 4447 AN XY: 37196

Gnomad4 AFR exome AF: 0.253

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.0176

Gnomad4 SAS exome AF: 0.0670

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.155 AC: 23517 AN: 152156 Hom.: 2150 Cov.: 32 AF XY: 0.154 AC XY: 11443 AN XY: 74398

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.0258

Gnomad4 SAS AF: 0.0689

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.161

Alfa AF: 0.126 Hom.: 2699

Bravo AF: 0.161

Asia WGS AF: 0.0790 AC: 274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.61
DANN	Benign	0.20

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: rs6853; hg19: chr3-38184370;