chr7-128939612-G-A

Variant names:

• chr7-128939612-G-A
• rs3823536
• NM_001098629.3:c.-12+1563G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001098629.3(IRF5):​c.-12+1563G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,026 control chromosomes in the GnomAD database, including 12,968 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.40 (12968 hom., cov: 33)
• Consequence: IRF5 NM_001098629.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.17
• Publications: 23 publications found

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]

IRF5 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-128939612-G-A is Benign according to our data. Variant chr7-128939612-G-A is described in ClinVar as [Benign]. Clinvar id is 1262643.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF5	NM_001098629.3	c.-12+1563G>A		intron_variant	Intron 1 of 8	ENST00000357234.10	NP_001092099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF5	ENST00000357234.10	c.-12+1563G>A		intron_variant	Intron 1 of 8	1	NM_001098629.3	ENSP00000349770.5

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61115 AN: 151908 Hom.: 12967 Cov.: 33

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.450

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.402 AC: 61138 AN: 152026 Hom.: 12968 Cov.: 33 AF XY: 0.397 AC XY: 29504 AN XY: 74320

African (AFR) AF: 0.302 AC: 12530 AN: 41464

American (AMR) AF: 0.413 AC: 6317 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2019 AN: 3470

East Asian (EAS) AF: 0.187 AC: 967 AN: 5170

South Asian (SAS) AF: 0.433 AC: 2086 AN: 4822

European-Finnish (FIN) AF: 0.410 AC: 4340 AN: 10578

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31364 AN: 67926

Other (OTH) AF: 0.447 AC: 943 AN: 2110

Alfa AF: 0.436 Hom.: 2653

Bravo AF: 0.399

Asia WGS AF: 0.288 AC: 1006 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 18, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 31659207) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.72
PhyloP100		-2.2
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: rs3823536; hg19: chr7-128579666;