7-128939612-G-A

Position:

• chr7-128939612-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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/exons	MANE	Protein	UniProt
IRF5	NM_001098629.3	c.-12+1563G>A		intron_variant		ENST00000357234.10	NP_001092099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF5	ENST00000357234.10	c.-12+1563G>A		intron_variant		1	NM_001098629.3	ENSP00000349770

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

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.447

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 18, 2020

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

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: rs3823536; hg19: chr7-128579666;