rs7744

Variant names:

• chr3-38142530-A-G
• rs7744
• ENST00000416282.3:n.2238A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-38142530-A-G
• chr3-38142530-A-T

Variant summary

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

The ENST00000416282.3(MYD88):​n.2238A>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 0.145 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 ENST00000416282.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370
• Publications: 72 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=-0.9).
• 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 rank	MANE	Protein	UniProt
MYD88	NM_002468.5	c.*1244A>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000650905.2	NP_002459.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYD88	ENST00000650905.2	c.*1244A>G		3_prime_UTR_variant	Exon 5 of 5		NM_002468.5	ENSP00000498360.2

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

African (AFR) AF: 0.0462 AC: 180 AN: 3896

American (AMR) AF: 0.177 AC: 442 AN: 2500

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 779 AN: 5124

East Asian (EAS) AF: 0.320 AC: 3654 AN: 11408

South Asian (SAS) AF: 0.0997 AC: 70 AN: 702

European-Finnish (FIN) AF: 0.194 AC: 12 AN: 62

Middle Eastern (MID) AF: 0.0407 AC: 20 AN: 492

European-Non Finnish (NFE) AF: 0.146 AC: 7312 AN: 50034

Other (OTH) AF: 0.128 AC: 869 AN: 6772

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

African (AFR) AF: 0.0456 AC: 1896 AN: 41542

American (AMR) AF: 0.188 AC: 2880 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 513 AN: 3466

East Asian (EAS) AF: 0.352 AC: 1816 AN: 5166

South Asian (SAS) AF: 0.0966 AC: 465 AN: 4816

European-Finnish (FIN) AF: 0.197 AC: 2086 AN: 10568

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10484 AN: 67990

Other (OTH) AF: 0.121 AC: 256 AN: 2108

Alfa AF: 0.146 Hom.: 3065

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
PhyloP100		-0.37
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: rs7744; hg19: chr3-38184021;