rs4579

chr3-37053188-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.*663C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,328 control chromosomes in the GnomAD database, including 10,573 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 0.35 (10539 hom., cov: 31)
  • Exomes 𝑓: 0.37 (34 hom.)
• Consequence: LRRFIP2 NM_006309.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15

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=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRFIP2	NM_006309.4	c.*663C>T		3_prime_UTR_variant	28/28	ENST00000336686.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRFIP2	ENST00000336686.9	c.*663C>T		3_prime_UTR_variant	28/28	1	NM_006309.4
LRRFIP2	ENST00000354379.8	c.*663C>T		3_prime_UTR_variant	14/14	1		P1
LRRFIP2	ENST00000460646.5	n.2673C>T		non_coding_transcript_exon_variant	5/5	1
LRRFIP2	ENST00000421276.6	c.*663C>T		3_prime_UTR_variant	15/15	2

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53332 AN: 151734 Hom.: 10532 Cov.: 31

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.0772

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.347

GnomAD4 exome AF: 0.369 AC: 175 AN: 474 Hom.: 34 Cov.: 0 AF XY: 0.348 AC XY: 98 AN XY: 282

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.383

Gnomad4 NFE exome AF: 0.225

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.351 AC: 53346 AN: 151854 Hom.: 10539 Cov.: 31 AF XY: 0.345 AC XY: 25584 AN XY: 74236

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.0772

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.344

Alfa AF: 0.415 Hom.: 5588

Bravo AF: 0.346

Asia WGS AF: 0.181 AC: 636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	13
Dann	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs4579; hg19: chr3-37094679;