chr7-128939993-G-T

Position:

• chr7-128939993-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098629.3(IRF5):​c.-12+1944G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 151,572 control chromosomes in the GnomAD database, including 13,378 homozygotes. 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: 𝑓 0.41 (13378 hom., cov: 32)
• Consequence: IRF5 NM_001098629.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF5	NM_001098629.3	c.-12+1944G>T		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+1944G>T		intron_variant		1	NM_001098629.3	ENSP00000349770.5

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62635 AN: 151452 Hom.: 13374 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.413 AC: 62664 AN: 151572 Hom.: 13378 Cov.: 32 AF XY: 0.407 AC XY: 30194 AN XY: 74096

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.459

Alfa AF: 0.434 Hom.: 1799

Bravo AF: 0.413

Asia WGS AF: 0.298 AC: 1040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.78

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: rs3778752; hg19: chr7-128580047;