5-132485305-G-A

Variant names:

• chr5-132485305-G-A
• rs17622656
• NM_002198.3:c.717+362C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002198.3(IRF1):​c.717+362C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 223,062 control chromosomes in the GnomAD database, including 10,258 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 0.25 (6142 hom., cov: 34)
  • Exomes 𝑓: 0.31 (4116 hom.)
• Consequence: IRF1 NM_002198.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.454
• Publications: 36 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF1	NM_002198.3	MANE Select	c.717+362C>T		intron	N/A	NP_002189.1
	IRF1	NM_001354924.1		c.594+362C>T		intron	N/A	NP_001341853.1
	IRF1	NM_001354925.1		c.667+946C>T		intron	N/A	NP_001341854.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF1	ENST00000245414.9	TSL:1 MANE Select	c.717+362C>T		intron	N/A	ENSP00000245414.4
	ENSG00000283782	ENST00000638452.2	TSL:5	c.-169+35616G>A		intron	N/A	ENSP00000492349.2
	CARINH	ENST00000612967.2	TSL:1	n.281-887G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38200 AN: 152098 Hom.: 6142 Cov.: 34

Gnomad AFR AF: 0.0889

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0854

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.305

GnomAD4 exome AF: 0.307 AC: 21759 AN: 70846 Hom.: 4116 Cov.: 0 AF XY: 0.301 AC XY: 11171 AN XY: 37068

African (AFR) AF: 0.0947 AC: 258 AN: 2724

American (AMR) AF: 0.245 AC: 1048 AN: 4272

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 852 AN: 2646

East Asian (EAS) AF: 0.000941 AC: 5 AN: 5314

South Asian (SAS) AF: 0.0944 AC: 489 AN: 5180

European-Finnish (FIN) AF: 0.252 AC: 756 AN: 3000

Middle Eastern (MID) AF: 0.196 AC: 61 AN: 312

European-Non Finnish (NFE) AF: 0.394 AC: 16888 AN: 42888

Other (OTH) AF: 0.311 AC: 1402 AN: 4510

GnomAD4 genome AF: 0.251 AC: 38192 AN: 152216 Hom.: 6142 Cov.: 34 AF XY: 0.240 AC XY: 17876 AN XY: 74406

African (AFR) AF: 0.0886 AC: 3682 AN: 41548

American (AMR) AF: 0.277 AC: 4245 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1094 AN: 3472

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5190

South Asian (SAS) AF: 0.0854 AC: 412 AN: 4822

European-Finnish (FIN) AF: 0.257 AC: 2721 AN: 10590

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.365 AC: 24821 AN: 67980

Other (OTH) AF: 0.301 AC: 635 AN: 2112

Alfa AF: 0.322 Hom.: 12285

Bravo AF: 0.251

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.6
DANN	Benign	0.64
PhyloP100		0.45
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: rs17622656; hg19: chr5-131820997; COSMIC: COSV55376693; COSMIC: COSV55376693;