3-37053579-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006309.4(LRRFIP2):c.*272G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 351,748 control chromosomes in the GnomAD database, including 42,197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

• Frequency:
  • Genomes: 𝑓 0.50 (20234 hom., cov: 31)
  • Exomes 𝑓: 0.45 (21963 hom.)
• Consequence: LRRFIP2 NM_006309.4 3_prime_UTR
• Clinical Significance: Benign reviewed by expert panel B:1
• Conservation: PhyloP100: 0.414

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 3-37053579-C-T is Benign according to our data. Variant chr3-37053579-C-T is described in ClinVar as [Benign]. Clinvar id is 89585.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr3-37053579-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRFIP2	NM_006309.4	c.*272G>A		3_prime_UTR_variant	28/28	ENST00000336686.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRFIP2	ENST00000336686.9	c.*272G>A		3_prime_UTR_variant	28/28	1	NM_006309.4
LRRFIP2	ENST00000354379.8	c.*272G>A		3_prime_UTR_variant	14/14	1		P1
LRRFIP2	ENST00000460646.5	n.2282G>A		non_coding_transcript_exon_variant	5/5	1
LRRFIP2	ENST00000421276.6	c.*272G>A		3_prime_UTR_variant	15/15	2

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76428 AN: 151810 Hom.: 20212 Cov.: 31

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.0968

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.488

GnomAD4 exome AF: 0.449 AC: 89624 AN: 199818 Hom.: 21963 Cov.: 0 AF XY: 0.435 AC XY: 46033 AN XY: 105884

Gnomad4 AFR exome AF: 0.596

Gnomad4 AMR exome AF: 0.430

Gnomad4 ASJ exome AF: 0.438

Gnomad4 EAS exome AF: 0.128

Gnomad4 SAS exome AF: 0.268

Gnomad4 FIN exome AF: 0.427

Gnomad4 NFE exome AF: 0.511

Gnomad4 OTH exome AF: 0.464

GnomAD4 genome AF: 0.504 AC: 76501 AN: 151930 Hom.: 20234 Cov.: 31 AF XY: 0.494 AC XY: 36709 AN XY: 74258

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.0969

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.482

Alfa AF: 0.499 Hom.: 31503

Bravo AF: 0.511

Asia WGS AF: 0.234 AC: 820 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: reviewed by expert panel

Submissions by phenotype

Lynch syndrome Benign:1

Benign, reviewed by expert panel

research

International Society for Gastrointestinal Hereditary Tumours (InSiGHT)

Sep 05, 2013

MAF >1% -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	8.7
Dann	Benign	0.81
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: rs10849; hg19: chr3-37095070;