rs4988457

Positions:

• chr3-38140645-C-G

Variant summary

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

The NM_002468.5(MYD88):​c.644+77C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0452 in 1,605,522 control chromosomes in the GnomAD database, including 1,840 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 0.057 (267 hom., cov: 33)
  • Exomes 𝑓: 0.044 (1573 hom.)
• Consequence: MYD88 NM_002468.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYD88	NM_002468.5	c.644+77C>G		intron_variant		ENST00000650905.2	NP_002459.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYD88	ENST00000650905.2	c.644+77C>G		intron_variant			NM_002468.5	ENSP00000498360	A1

Frequencies

GnomAD3 genomes AF: 0.0569 AC: 8660 AN: 152064 Hom.: 267 Cov.: 33

Gnomad AFR AF: 0.0858

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0434

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.0814

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.0462

Gnomad OTH AF: 0.0565

GnomAD4 exome AF: 0.0440 AC: 63912 AN: 1453340 Hom.: 1573 Cov.: 28 AF XY: 0.0432 AC XY: 31255 AN XY: 723630

Gnomad4 AFR exome AF: 0.0885

Gnomad4 AMR exome AF: 0.0319

Gnomad4 ASJ exome AF: 0.0371

Gnomad4 EAS exome AF: 0.00492

Gnomad4 SAS exome AF: 0.0191

Gnomad4 FIN exome AF: 0.0732

Gnomad4 NFE exome AF: 0.0448

Gnomad4 OTH exome AF: 0.0454

GnomAD4 genome AF: 0.0570 AC: 8671 AN: 152182 Hom.: 267 Cov.: 33 AF XY: 0.0576 AC XY: 4287 AN XY: 74388

Gnomad4 AFR AF: 0.0859

Gnomad4 AMR AF: 0.0433

Gnomad4 ASJ AF: 0.0424

Gnomad4 EAS AF: 0.0106

Gnomad4 SAS AF: 0.0149

Gnomad4 FIN AF: 0.0814

Gnomad4 NFE AF: 0.0462

Gnomad4 OTH AF: 0.0564

Alfa AF: 0.0539 Hom.: 29

Bravo AF: 0.0557

Asia WGS AF: 0.0190 AC: 65 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.1
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs4988457; hg19: chr3-38182136;