rs6853

Variant names:

• chr3-38142879-A-G
• rs6853
• NM_002468.5:c.*1593A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-38142879-A-G
• chr3-38142879-A-T

Variant summary

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

The NM_002468.5(MYD88):​c.*1593A>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 0.142 in 233,104 control chromosomes in the GnomAD database, including 2,853 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 0.15 (2150 hom., cov: 32)
  • Exomes 𝑓: 0.12 (703 hom.)
• Consequence: MYD88 NM_002468.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287
• Publications: 66 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002468.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYD88	NM_002468.5	MANE Select	c.*1593A>G		3_prime_UTR	Exon 5 of 5	NP_002459.3	Q99836-1
	MYD88	NM_001172567.2		c.*1593A>G		3_prime_UTR	Exon 5 of 5	NP_001166038.2	Q99836-6
	MYD88	NM_001172568.2		c.*1593A>G		3_prime_UTR	Exon 4 of 4	NP_001166039.2	Q99836-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYD88	ENST00000650905.2	MANE Select	c.*1593A>G		3_prime_UTR	Exon 5 of 5	ENSP00000498360.2	Q99836-1
	MYD88	ENST00000421516.3	TSL:1	c.*1593A>G		3_prime_UTR	Exon 5 of 5	ENSP00000391753.3	Q99836-6
	MYD88	ENST00000417037.8	TSL:1	c.*1593A>G		3_prime_UTR	Exon 4 of 4	ENSP00000401399.4	Q99836-2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23489 AN: 152038 Hom.: 2141 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0257

Gnomad SAS AF: 0.0691

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.119 AC: 9663 AN: 80948 Hom.: 703 Cov.: 0 AF XY: 0.120 AC XY: 4447 AN XY: 37196

African (AFR) AF: 0.253 AC: 987 AN: 3894

American (AMR) AF: 0.111 AC: 278 AN: 2498

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 804 AN: 5126

East Asian (EAS) AF: 0.0176 AC: 201 AN: 11408

South Asian (SAS) AF: 0.0670 AC: 47 AN: 702

European-Finnish (FIN) AF: 0.133 AC: 8 AN: 60

Middle Eastern (MID) AF: 0.262 AC: 129 AN: 492

European-Non Finnish (NFE) AF: 0.125 AC: 6258 AN: 50002

Other (OTH) AF: 0.141 AC: 951 AN: 6766

GnomAD4 genome AF: 0.155 AC: 23517 AN: 152156 Hom.: 2150 Cov.: 32 AF XY: 0.154 AC XY: 11443 AN XY: 74398

African (AFR) AF: 0.257 AC: 10652 AN: 41460

American (AMR) AF: 0.114 AC: 1737 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 544 AN: 3470

East Asian (EAS) AF: 0.0258 AC: 134 AN: 5192

South Asian (SAS) AF: 0.0689 AC: 333 AN: 4830

European-Finnish (FIN) AF: 0.122 AC: 1292 AN: 10588

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8295 AN: 68006

Other (OTH) AF: 0.161 AC: 341 AN: 2112

Alfa AF: 0.131 Hom.: 6653

Bravo AF: 0.161

Asia WGS AF: 0.0790 AC: 274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.61
DANN	Benign	0.20
PhyloP100		-0.29
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: rs6853; hg19: chr3-38184370;