rs3774327

Variant names:

• chr3-37057876-G-A
• rs3774327
• NM_006309.4:c.1870+914C>T

Variant summary

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

The ENST00000336686.9(LRRFIP2):​c.1870+914C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 152,034 control chromosomes in the GnomAD database, including 21,626 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 0.52 (21626 hom., cov: 32)
• Consequence: LRRFIP2 ENST00000336686.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620
• Publications: 7 publications found

Genes affected

LRRFIP2 (HGNC:6703): (LRR binding FLII interacting protein 2) The protein encoded by this gene, along with MYD88, binds to the cytosolic tail of toll-like receptor 4 (TLR4), which results in activation of nuclear factor kappa B signaling. The ubiquitin-like protein FAT10 prevents the interaction of the encoded protein and TLR4, thereby inactivating the nuclear factor kappa B signaling pathway. In addition, this protein can downregulate the NLRP3 inflammasome by recruiting the caspase-1 inhibitor Flightless-I to the inflammasome complex. [provided by RefSeq, Jan 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000336686.9. 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
	LRRFIP2	NM_006309.4	MANE Select	c.1870+914C>T		intron	N/A	NP_006300.1
	LRRFIP2	NM_001348297.1		c.1567+914C>T		intron	N/A	NP_001335226.1
	LRRFIP2	NM_001348298.1		c.1357+914C>T		intron	N/A	NP_001335227.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRFIP2	ENST00000336686.9	TSL:1 MANE Select	c.1870+914C>T		intron	N/A	ENSP00000338727.4
	LRRFIP2	ENST00000354379.8	TSL:1	c.907+914C>T		intron	N/A	ENSP00000346349.4
	LRRFIP2	ENST00000460646.5	TSL:1	n.1714+914C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78699 AN: 151916 Hom.: 21593 Cov.: 32

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.0983

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.518 AC: 78786 AN: 152034 Hom.: 21626 Cov.: 32 AF XY: 0.509 AC XY: 37789 AN XY: 74312

African (AFR) AF: 0.641 AC: 26587 AN: 41458

American (AMR) AF: 0.487 AC: 7427 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1551 AN: 3466

East Asian (EAS) AF: 0.0984 AC: 510 AN: 5184

South Asian (SAS) AF: 0.263 AC: 1272 AN: 4828

European-Finnish (FIN) AF: 0.430 AC: 4539 AN: 10544

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35187 AN: 67970

Other (OTH) AF: 0.497 AC: 1049 AN: 2112

Alfa AF: 0.524 Hom.: 4808

Bravo AF: 0.529

Asia WGS AF: 0.240 AC: 839 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.7
DANN	Benign	0.63
PhyloP100		-0.062
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: rs3774327; hg19: chr3-37099367;