rs749072

Positions:

• chr3-37054533-T-C

Variant summary

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

The NM_006309.4(LRRFIP2):​c.1951-18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,570,158 control chromosomes in the GnomAD database, including 64,235 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.27 (5983 hom., cov: 32)
  • Exomes 𝑓: 0.28 (58252 hom.)
• Consequence: LRRFIP2 NM_006309.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.09

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: This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRFIP2	NM_006309.4	c.1951-18A>G		intron_variant		ENST00000336686.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRFIP2	ENST00000336686.9	c.1951-18A>G		intron_variant		1	NM_006309.4

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40841 AN: 151948 Hom.: 5985 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.299

GnomAD3 exomes AF: 0.321 AC: 79649 AN: 247830 Hom.: 14350 AF XY: 0.323 AC XY: 43236 AN XY: 133834

Gnomad AFR exome AF: 0.213

Gnomad AMR exome AF: 0.354

Gnomad ASJ exome AF: 0.352

Gnomad EAS exome AF: 0.615

Gnomad SAS exome AF: 0.400

Gnomad FIN exome AF: 0.289

Gnomad NFE exome AF: 0.262

Gnomad OTH exome AF: 0.321

GnomAD4 exome AF: 0.278 AC: 393663 AN: 1418092 Hom.: 58252 Cov.: 24 AF XY: 0.281 AC XY: 199127 AN XY: 707622

Gnomad4 AFR exome AF: 0.212

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.353

Gnomad4 EAS exome AF: 0.577

Gnomad4 SAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.289

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.301

GnomAD4 genome AF: 0.269 AC: 40864 AN: 152066 Hom.: 5983 Cov.: 32 AF XY: 0.275 AC XY: 20437 AN XY: 74334

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.300

Alfa AF: 0.270 Hom.: 2363

Bravo AF: 0.271

Asia WGS AF: 0.485 AC: 1683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.021
DANN	Benign	0.69
BranchPoint Hunter		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: rs749072; hg19: chr3-37096024; COSMIC: COSV51614379; COSMIC: COSV51614379;