rs1141168

Variant names:

• chr12-43788903-A-G
• rs1141168
• NM_016123.4:c.*2188A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-43788903-A-G
• chr12-43788903-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016123.4(IRAK4):​c.*2188A>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 0.429 in 151,854 control chromosomes in the GnomAD database, including 14,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14413 hom., cov: 30)
  • Exomes 𝑓: 0.45 (3 hom.)
• Consequence: IRAK4 NM_016123.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.301
• Publications: 15 publications found

Genes affected

IRAK4 (HGNC:17967): (interleukin 1 receptor associated kinase 4) This gene encodes a kinase that activates NF-kappaB in both the Toll-like receptor (TLR) and T-cell receptor (TCR) signaling pathways. The protein is essential for most innate immune responses. Mutations in this gene result in IRAK4 deficiency and recurrent invasive pneumococcal disease. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

IRAK4 Gene-Disease associations (from GenCC):

• immunodeficiency 67

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 12-43788903-A-G is Benign according to our data. Variant chr12-43788903-A-G is described in ClinVar as Benign. ClinVar VariationId is 308762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016123.4. 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
	IRAK4	NM_016123.4	MANE Select	c.*2188A>G		3_prime_UTR	Exon 12 of 12	NP_057207.2
	IRAK4	NM_001114182.3		c.*2188A>G		3_prime_UTR	Exon 13 of 13	NP_001107654.1
	IRAK4	NM_001351345.2		c.*2188A>G		3_prime_UTR	Exon 13 of 13	NP_001338274.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRAK4	ENST00000613694.5	TSL:1 MANE Select	c.*2188A>G		3_prime_UTR	Exon 12 of 12	ENSP00000479889.3
	IRAK4	ENST00000696791.1		n.*3473A>G		non_coding_transcript_exon	Exon 13 of 13	ENSP00000512873.1
	IRAK4	ENST00000696792.1		n.*2316A>G		non_coding_transcript_exon	Exon 5 of 5	ENSP00000512874.1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65100 AN: 151714 Hom.: 14413 Cov.: 30

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.428

GnomAD4 exome AF: 0.455 AC: 10 AN: 22 Hom.: 3 Cov.: 0 AF XY: 0.583 AC XY: 7 AN XY: 12

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.455 AC: 10 AN: 22

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.429 AC: 65108 AN: 151832 Hom.: 14413 Cov.: 30 AF XY: 0.434 AC XY: 32166 AN XY: 74198

African (AFR) AF: 0.303 AC: 12535 AN: 41392

American (AMR) AF: 0.421 AC: 6425 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1887 AN: 3466

East Asian (EAS) AF: 0.513 AC: 2638 AN: 5144

South Asian (SAS) AF: 0.517 AC: 2495 AN: 4822

European-Finnish (FIN) AF: 0.511 AC: 5373 AN: 10518

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32369 AN: 67912

Other (OTH) AF: 0.429 AC: 907 AN: 2114

Alfa AF: 0.462 Hom.: 41791

Bravo AF: 0.414

Asia WGS AF: 0.509 AC: 1769 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Immunodeficiency 67 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.4
DANN	Benign	0.83
PhyloP100		0.30
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: rs1141168; hg19: chr12-44182706;