rs148928811

Variant names:

• chr7-128942097-C-A
• NM_001098629.3:c.16C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-128942097-C-A
• chr7-128942097-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001098629.3(IRF5):​c.16C>A​(p.Pro6Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,456,504 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: IRF5 NM_001098629.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.603

Genes affected

IRF5 (HGNC:6120): (interferon regulatory factor 5) This gene encodes a member of the interferon regulatory factor (IRF) family, a group of transcription factors with diverse roles, including virus-mediated activation of interferon, and modulation of cell growth, differentiation, apoptosis, and immune system activity. Members of the IRF family are characterized by a conserved N-terminal DNA-binding domain containing tryptophan (W) repeats. Alternative promoter use and alternative splicing result in multiple transcript variants, and a 30-nt indel polymorphism (SNP rs60344245) can result in loss of a 10-aa segment. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2500438).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF5	NM_001098629.3	c.16C>A	p.Pro6Thr	missense_variant	Exon 2 of 9	ENST00000357234.10	NP_001092099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF5	ENST00000357234.10	c.16C>A	p.Pro6Thr	missense_variant	Exon 2 of 9	1	NM_001098629.3	ENSP00000349770.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1456504 Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3 AN XY: 724312

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.087	.;.;.;.;T;T;T;T;T;T;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.79	.;T;T;T;T;T;.;T;T;.;T
M_CAP	Pathogenic	0.59	D
MetaRNN	Benign	0.25	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Uncertain	2.3	M;.;M;M;.;.;M;M;.;M;M
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.94	N;.;N;N;N;N;N;N;N;N;.
REVEL	Uncertain	0.45
Sift	Benign	0.21	T;.;D;D;T;T;D;D;T;D;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D;D
Polyphen		0.68	P;.;P;.;.;.;P;P;.;P;.
Vest4		0.32, 0.35, 0.36, 0.30, 0.31, 0.29
MutPred		0.37		Gain of catalytic residue at M1 (P = 0.0274);Gain of catalytic residue at M1 (P = 0.0274);Gain of catalytic residue at M1 (P = 0.0274);Gain of catalytic residue at M1 (P = 0.0274);Gain of catalytic residue at M1 (P = 0.0274);Gain of catalytic residue at M1 (P = 0.0274);Gain of catalytic residue at M1 (P = 0.0274);Gain of catalytic residue at M1 (P = 0.0274);Gain of catalytic residue at M1 (P = 0.0274);Gain of catalytic residue at M1 (P = 0.0274);Gain of catalytic residue at M1 (P = 0.0274);
MVP		0.83
MPC		1.1
ClinPred		0.37	T
GERP RS		3.0
Varity_R		0.067
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-128582151;