rs4988457

Variant names:

• chr3-38140645-C-G
• rs4988457
• ENST00000416282.3:n.636C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000416282.3(MYD88):​n.636C>G variant causes a non coding transcript exon 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 ENST00000416282.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• Publications: 20 publications found

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 Gene-Disease associations (from GenCC):

• pyogenic bacterial infections due to MyD88 deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000416282.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYD88	NM_002468.5	MANE Select	c.644+77C>G		intron	N/A	NP_002459.3
	MYD88	NM_001172567.2		c.668+53C>G		intron	N/A	NP_001166038.2
	MYD88	NM_001172568.2		c.509+77C>G		intron	N/A	NP_001166039.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYD88	ENST00000416282.3	TSL:1	n.636C>G		non_coding_transcript_exon	Exon 2 of 3
	MYD88	ENST00000650905.2	MANE Select	c.644+77C>G		intron	N/A	ENSP00000498360.2
	MYD88	ENST00000421516.3	TSL:1	c.668+53C>G		intron	N/A	ENSP00000391753.3

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

African (AFR) AF: 0.0885 AC: 2946 AN: 33278

American (AMR) AF: 0.0319 AC: 1426 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0371 AC: 967 AN: 26082

East Asian (EAS) AF: 0.00492 AC: 195 AN: 39658

South Asian (SAS) AF: 0.0191 AC: 1647 AN: 86080

European-Finnish (FIN) AF: 0.0732 AC: 3905 AN: 53350

Middle Eastern (MID) AF: 0.103 AC: 589 AN: 5730

European-Non Finnish (NFE) AF: 0.0448 AC: 49509 AN: 1104372

Other (OTH) AF: 0.0454 AC: 2728 AN: 60088

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

African (AFR) AF: 0.0859 AC: 3566 AN: 41492

American (AMR) AF: 0.0433 AC: 663 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0424 AC: 147 AN: 3470

East Asian (EAS) AF: 0.0106 AC: 55 AN: 5180

South Asian (SAS) AF: 0.0149 AC: 72 AN: 4828

European-Finnish (FIN) AF: 0.0814 AC: 862 AN: 10596

Middle Eastern (MID) AF: 0.140 AC: 41 AN: 292

European-Non Finnish (NFE) AF: 0.0462 AC: 3144 AN: 68000

Other (OTH) AF: 0.0564 AC: 119 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.1
DANN	Benign	0.72
PhyloP100		-0.041
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs4988457; hg19: chr3-38182136;