dbSNP rs4579: LRRFIP2:c.*663C>T (chr3-37053188-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.15

Publications

15 publications found

Variant links:

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]

LRRFIP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006309.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LRRFIP2	NM_006309.4	MANE Select	c.*663C>T	3_prime_UTR	Exon 28 of 28	NP_006300.1	Q9Y608-1
LRRFIP2	NM_001348297.1		c.*663C>T	3_prime_UTR	Exon 24 of 24	NP_001335226.1
LRRFIP2	NM_001348298.1		c.*663C>T	3_prime_UTR	Exon 22 of 22	NP_001335227.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LRRFIP2	ENST00000336686.9	TSL:1 MANE Select	c.*663C>T	3_prime_UTR	Exon 28 of 28	ENSP00000338727.4	Q9Y608-1
LRRFIP2	ENST00000354379.8	TSL:1	c.*663C>T	3_prime_UTR	Exon 14 of 14	ENSP00000346349.4	Q9Y608-2
LRRFIP2	ENST00000460646.5	TSL:1	n.2673C>T	non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

53332

AN:

151734

Hom.:

10532

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.348

AC XY:

AN XY:

282

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.383

AC:

164

AN:

428

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.225

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.351

AC:

53346

AN:

151854

Hom.:

10539

Cov.:

AF XY:

0.345

AC XY:

25584

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.209

AC:

8663

AN:

41420

American (AMR)

AF:

0.388

AC:

5923

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.405

AC:

1403

AN:

3466

East Asian (EAS)

AF:

0.0772

AC:

399

AN:

5166

South Asian (SAS)

AF:

0.222

AC:

1063

AN:

4792

European-Finnish (FIN)

AF:

0.364

AC:

3832

AN:

10520

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.453

AC:

30757

AN:

67902

Other (OTH)

AF:

0.344

AC:

725

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1656

3313

4969

6626

8282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

502

1004

1506

2008

2510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.412

Hom.:

6603

Bravo

AF:

0.346

Asia WGS

AF:

0.181

AC:

636

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over