rs7744

Positions:

• chr3-38142530-A-G
• chr3-38142530-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.*1244A>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 0.145 in 233,144 control chromosomes in the GnomAD database, including 3,083 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 0.13 (1759 hom., cov: 32)
  • Exomes 𝑓: 0.16 (1324 hom.)
• Consequence: MYD88 NM_002468.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYD88	NM_002468.5	c.*1244A>G		3_prime_UTR_variant	5/5	ENST00000650905.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYD88	ENST00000650905.2	c.*1244A>G		3_prime_UTR_variant	5/5		NM_002468.5	A1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20462 AN: 152036 Hom.: 1761 Cov.: 32

Gnomad AFR AF: 0.0457

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.0963

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.123

GnomAD4 exome AF: 0.165 AC: 13338 AN: 80990 Hom.: 1324 Cov.: 0 AF XY: 0.163 AC XY: 6068 AN XY: 37220

Gnomad4 AFR exome AF: 0.0462

Gnomad4 AMR exome AF: 0.177

Gnomad4 ASJ exome AF: 0.152

Gnomad4 EAS exome AF: 0.320

Gnomad4 SAS exome AF: 0.0997

Gnomad4 FIN exome AF: 0.194

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.128

GnomAD4 genome AF: 0.134 AC: 20461 AN: 152154 Hom.: 1759 Cov.: 32 AF XY: 0.136 AC XY: 10132 AN XY: 74374

Gnomad4 AFR AF: 0.0456

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.0966

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.121

Alfa AF: 0.145 Hom.: 2268

Bravo AF: 0.130

Asia WGS AF: 0.174 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.52
DANN	Benign	0.47
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: rs7744; hg19: chr3-38184021;