rs1010959827

Variant names:

• chr7-128947368-G-C
• rs1010959827
• NM_001098629.3:c.620G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-128947368-G-C
• chr7-128947368-G-T

Variant summary

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

The NM_001098629.3(IRF5):​c.620G>C​(p.Gly207Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IRF5 NM_001098629.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221

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=0.09800431).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF5	NM_001098629.3	c.620G>C	p.Gly207Ala	missense_variant	Exon 6 of 9	ENST00000357234.10	NP_001092099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF5	ENST00000357234.10	c.620G>C	p.Gly207Ala	missense_variant	Exon 6 of 9	1	NM_001098629.3	ENSP00000349770.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1457744 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 725066

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	3.0
DANN	Benign	0.95
DEOGEN2	Benign	0.20	.;.;T;T;T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.78	.;T;.;T;.
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.098	T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.7	.;.;L;L;L
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.90	.;N;N;N;N
REVEL	Benign	0.29
Sift	Benign	0.057	.;T;T;T;T
Sift4G	Benign	1.0	.;T;T;T;T
Polyphen		0.012	B;B;B;B;B
Vest4		0.23, 0.23, 0.22, 0.22
MutPred		0.30		.;.;Loss of catalytic residue at P187 (P = 0.113);Loss of catalytic residue at P187 (P = 0.113);Loss of catalytic residue at P187 (P = 0.113);
MVP		0.79
MPC		0.011
ClinPred		0.11	T
GERP RS		3.0
Varity_R		0.038
gMVP		0.47

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

LitVar

Other links and lift over

dbSNP: rs1010959827; hg19: chr7-128587422;