NM_002198.3:c.853+77G>A

Variant names:

• chr5-132484285-C-T
• rs2070728
• NM_002198.3:c.853+77G>A

Variant summary

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

The NM_002198.3(IRF1):​c.853+77G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 1,517,494 control chromosomes in the GnomAD database, including 85,718 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11085 hom., cov: 31)
  • Exomes 𝑓: 0.33 (74633 hom.)
• Consequence: IRF1 NM_002198.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.183
• Publications: 21 publications found

Genes affected

IRF1 (HGNC:6116): (interferon regulatory factor 1) The protein encoded by this gene is a transcriptional regulator and tumor suppressor, serving as an activator of genes involved in both innate and acquired immune responses. The encoded protein activates the transcription of genes involved in the body's response to viruses and bacteria, playing a role in cell proliferation, apoptosis, the immune response, and DNA damage response. This protein represses the transcription of several other genes. As a tumor suppressor, it both suppresses tumor cell growth and stimulates an immune response against tumor cells. Defects in this gene have been associated with gastric cancer, myelogenous leukemia, and lung cancer. [provided by RefSeq, Aug 2017]

ENSG00000283782 (HGNC:):

CARINH (HGNC:33838): (colitis associated IRF1 antisense regulator of intestinal homeostasis)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 5-132484285-C-T is Benign according to our data. Variant chr5-132484285-C-T is described in ClinVar as Benign. ClinVar VariationId is 2688399.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002198.3. 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
	IRF1	NM_002198.3	MANE Select	c.853+77G>A		intron	N/A	NP_002189.1	P10914
	IRF1	NM_001354924.1		c.730+77G>A		intron	N/A	NP_001341853.1	X5D3F6
	IRF1	NM_001354925.1		c.668-210G>A		intron	N/A	NP_001341854.1	A0A7P0TAL6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF1	ENST00000245414.9	TSL:1 MANE Select	c.853+77G>A		intron	N/A	ENSP00000245414.4	P10914
	ENSG00000283782	ENST00000638452.2	TSL:5	c.-169+34596C>T		intron	N/A	ENSP00000492349.2	A0A1W2PQ90
	CARINH	ENST00000612967.2	TSL:1	n.281-1907C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.376 AC: 56982 AN: 151372 Hom.: 11071 Cov.: 31

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.359

GnomAD4 exome AF: 0.327 AC: 447316 AN: 1366004 Hom.: 74633 Cov.: 23 AF XY: 0.329 AC XY: 222980 AN XY: 678514

African (AFR) AF: 0.478 AC: 14629 AN: 30614

American (AMR) AF: 0.317 AC: 12790 AN: 40370

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 6878 AN: 23138

East Asian (EAS) AF: 0.328 AC: 12784 AN: 38996

South Asian (SAS) AF: 0.375 AC: 29590 AN: 78984

European-Finnish (FIN) AF: 0.325 AC: 16764 AN: 51538

Middle Eastern (MID) AF: 0.391 AC: 2097 AN: 5370

European-Non Finnish (NFE) AF: 0.320 AC: 332621 AN: 1040198

Other (OTH) AF: 0.337 AC: 19163 AN: 56796

GnomAD4 genome AF: 0.377 AC: 57039 AN: 151490 Hom.: 11085 Cov.: 31 AF XY: 0.375 AC XY: 27764 AN XY: 73982

African (AFR) AF: 0.484 AC: 19951 AN: 41194

American (AMR) AF: 0.342 AC: 5215 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1100 AN: 3456

East Asian (EAS) AF: 0.358 AC: 1830 AN: 5118

South Asian (SAS) AF: 0.409 AC: 1970 AN: 4812

European-Finnish (FIN) AF: 0.327 AC: 3443 AN: 10536

Middle Eastern (MID) AF: 0.479 AC: 139 AN: 290

European-Non Finnish (NFE) AF: 0.331 AC: 22429 AN: 67822

Other (OTH) AF: 0.359 AC: 755 AN: 2104

Alfa AF: 0.367 Hom.: 1342

Bravo AF: 0.381

Asia WGS AF: 0.376 AC: 1306 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.6
DANN	Benign	0.74
PhyloP100		-0.18
PromoterAI		-0.041	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs2070728; hg19: chr5-131819977; COSMIC: COSV55376084; COSMIC: COSV55376084;