NM_001572.5:c.1357-43A>C

Variant names:

• chr11-612843-T-G
• rs10902178
• NM_001572.5:c.1357-43A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001572.5(IRF7):​c.1357-43A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,597,786 control chromosomes in the GnomAD database, including 64,101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (9371 hom., cov: 31)
  • Exomes 𝑓: 0.27 (54730 hom.)
• Consequence: IRF7 NM_001572.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.218
• Publications: 20 publications found

Genes affected

IRF7 (HGNC:6122): (interferon regulatory factor 7) This gene encodes interferon regulatory factor 7, a member of the interferon regulatory transcription factor (IRF) family. It has been shown to play a role in the transcriptional activation of virus-inducible cellular genes, including interferon beta chain genes. Inducible expression of IRF7 is largely restricted to lymphoid tissue. The encoded protein plays an important role in the innate immune response against DNA and RNA viruses. [provided by RefSeq, Jul 2021]

IRF7 Gene-Disease associations (from GenCC):

• immunodeficiency 39

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 11-612843-T-G is Benign according to our data. Variant chr11-612843-T-G is described in ClinVar as Benign. ClinVar VariationId is 1185462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001572.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF7	NM_001572.5	MANE Select	c.1357-43A>C		intron	N/A	NP_001563.2
	IRF7	NM_004031.4		c.1396-43A>C		intron	N/A	NP_004022.2	Q92985-4
	IRF7	NM_001440440.1		c.1393-43A>C		intron	N/A	NP_001427369.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF7	ENST00000525445.6	TSL:5 MANE Select	c.1357-43A>C		intron	N/A	ENSP00000434009.2	Q92985-1
	IRF7	ENST00000397566.5	TSL:1	c.1396-43A>C		intron	N/A	ENSP00000380697.1	Q92985-4
	IRF7	ENST00000397570.5	TSL:1	c.1309-43A>C		intron	N/A	ENSP00000380700.2	M9RSF4

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49287 AN: 151568 Hom.: 9355 Cov.: 31

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.0258

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.333

GnomAD2 exomes AF: 0.255 AC: 61646 AN: 241498 AF XY: 0.244

Gnomad AFR exome AF: 0.522

Gnomad AMR exome AF: 0.323

Gnomad ASJ exome AF: 0.336

Gnomad EAS exome AF: 0.0281

Gnomad FIN exome AF: 0.190

Gnomad NFE exome AF: 0.267

Gnomad OTH exome AF: 0.261

GnomAD4 exome AF: 0.266 AC: 384082 AN: 1446098 Hom.: 54730 Cov.: 37 AF XY: 0.261 AC XY: 187489 AN XY: 718334

African (AFR) AF: 0.523 AC: 17413 AN: 33324

American (AMR) AF: 0.321 AC: 14306 AN: 44510

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 8717 AN: 26004

East Asian (EAS) AF: 0.0228 AC: 901 AN: 39478

South Asian (SAS) AF: 0.143 AC: 12309 AN: 86016

European-Finnish (FIN) AF: 0.198 AC: 9090 AN: 45828

Middle Eastern (MID) AF: 0.298 AC: 1503 AN: 5046

European-Non Finnish (NFE) AF: 0.274 AC: 303495 AN: 1106004

Other (OTH) AF: 0.273 AC: 16348 AN: 59888

GnomAD4 genome AF: 0.325 AC: 49338 AN: 151688 Hom.: 9371 Cov.: 31 AF XY: 0.314 AC XY: 23300 AN XY: 74116

African (AFR) AF: 0.519 AC: 21455 AN: 41328

American (AMR) AF: 0.307 AC: 4678 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1204 AN: 3472

East Asian (EAS) AF: 0.0258 AC: 133 AN: 5146

South Asian (SAS) AF: 0.128 AC: 615 AN: 4792

European-Finnish (FIN) AF: 0.185 AC: 1948 AN: 10540

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18321 AN: 67864

Other (OTH) AF: 0.331 AC: 697 AN: 2106

Alfa AF: 0.294 Hom.: 7967

Bravo AF: 0.346

Asia WGS AF: 0.125 AC: 437 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Immunodeficiency 39 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.5
DANN	Benign	0.65
PhyloP100		-0.22
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: rs10902178; hg19: chr11-612843; COSMIC: COSV52764777; COSMIC: COSV52764777;