rs3774327

Positions:

• chr3-37057876-G-A

Variant summary

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

The NM_006309.4(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 NM_006309.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRFIP2	NM_006309.4	c.1870+914C>T		intron_variant		ENST00000336686.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRFIP2	ENST00000336686.9	c.1870+914C>T		intron_variant		1	NM_006309.4

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

Gnomad4 AFR AF: 0.641

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.0984

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.497

Alfa AF: 0.521 Hom.: 4643

Bravo AF: 0.529

Asia WGS AF: 0.240 AC: 839 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.7
DANN	Benign	0.63

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: rs3774327; hg19: chr3-37099367;