Genetic Variant MYD88:n.636C>G (chr3-38140645-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0410

Publications

20 publications found

Variant links:

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)

MYD88 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYD88	NM_002468.5 link	c.644+77C>G		intron_variant	Intron 3 of 4	ENST00000650905.2	NP_002459.3	Q99836-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYD88	ENST00000650905.2 link	c.644+77C>G		intron_variant	Intron 3 of 4		NM_002468.5	ENSP00000498360.2		Q99836-1

Frequencies

GnomAD3 genomes

AF:

0.0569

AC:

8660

AN:

152064

Hom.:

267

Cov.:

show subpopulations

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.:

AF XY:

0.0432

AC XY:

31255

AN XY:

723630

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

3500

7000

10500

14000

17500

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0570

AC:

8671

AN:

152182

Hom.:

267

Cov.:

AF XY:

0.0576

AC XY:

4287

AN XY:

74388

show subpopulations

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:

AN:

5180

South Asian (SAS)

AF:

0.0149

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0814

AC:

862

AN:

10596

Middle Eastern (MID)

AF:

0.140

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0462

AC:

3144

AN:

68000

Other (OTH)

AF:

0.0564

AC:

119

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

424

849

1273

1698

2122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0539

Hom.:

Bravo

AF:

0.0557

Asia WGS

AF:

0.0190

AC:

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

(source)

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)

(source)

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

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chr3-38140645-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over