Genetic Variant ENST00000392000.4:c.2347C>G (chr2-237764060-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000392000.4(LRRFIP1):c.2347C>G(p.His783Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,613,890 control chromosomes in the GnomAD database, including 58,563 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 6816 hom., cov: 32)

Exomes 𝑓: 0.26 ( 51747 hom. )

Consequence

LRRFIP1
ENST00000392000.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.953

Publications

36 publications found

Variant links:

Genes affected

LRRFIP1 (HGNC:6702): (LRR binding FLII interacting protein 1) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and protein homodimerization activity. Involved in negative regulation of transcription by RNA polymerase II. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRFIP1 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

LRRFIP1 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 (MetaRNN=7.319268E-5).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRFIP1	NM_001137550.2 link	c.1459+3855C>G		intron_variant	Intron 19 of 23	ENST00000308482.14	NP_001131022.1	Q32MZ4-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRFIP1	ENST00000308482.14 link	c.1459+3855C>G		intron_variant	Intron 19 of 23	1	NM_001137550.2	ENSP00000310109.9		Q32MZ4-4

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

44271

AN:

151926

Hom.:

6799

Cov.:

show subpopulations

Gnomad AFR

AF:

0.352

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.308

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.531

Gnomad SAS

AF:

0.359

Gnomad FIN

AF:

0.284

Gnomad MID

AF:

0.344

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.266

GnomAD2 exomes

AF:

0.294

AC:

73913

AN:

251226

AF XY:

0.293

show subpopulations

Gnomad AFR exome

AF:

0.364

Gnomad AMR exome

AF:

0.305

Gnomad ASJ exome

AF:

0.239

Gnomad EAS exome

AF:

0.522

Gnomad FIN exome

AF:

0.272

Gnomad NFE exome

AF:

0.235

Gnomad OTH exome

AF:

0.274

GnomAD4 exome

AF:

0.257

AC:

375260

AN:

1461846

Hom.:

51747

Cov.:

AF XY:

0.260

AC XY:

188730

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.367

AC:

12290

AN:

33480

American (AMR)

AF:

0.305

AC:

13629

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

6286

AN:

26134

East Asian (EAS)

AF:

0.555

AC:

22044

AN:

39698

South Asian (SAS)

AF:

0.363

AC:

31325

AN:

86256

European-Finnish (FIN)

AF:

0.270

AC:

14447

AN:

53420

Middle Eastern (MID)

AF:

0.298

AC:

1721

AN:

5768

European-Non Finnish (NFE)

AF:

0.231

AC:

257333

AN:

1111980

Other (OTH)

AF:

0.268

AC:

16185

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

18061

36122

54184

72245

90306

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9088

18176

27264

36352

45440

<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:

0.292

AC:

44330

AN:

152044

Hom.:

6816

Cov.:

AF XY:

0.300

AC XY:

22313

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.353

AC:

14618

AN:

41442

American (AMR)

AF:

0.308

AC:

4711

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.233

AC:

808

AN:

3472

East Asian (EAS)

AF:

0.532

AC:

2753

AN:

5174

South Asian (SAS)

AF:

0.359

AC:

1734

AN:

4826

European-Finnish (FIN)

AF:

0.284

AC:

2996

AN:

10558

Middle Eastern (MID)

AF:

0.332

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.234

AC:

15916

AN:

67964

Other (OTH)

AF:

0.264

AC:

557

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1568

3135

4703

6270

7838

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

464

928

1392

1856

2320

<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:

0.252

Hom.:

3860

Bravo

AF:

0.293

TwinsUK

AF:

0.224

AC:

831

ALSPAC

AF:

0.228

AC:

880

ESP6500AA

AF:

0.371

AC:

1635

ESP6500EA

AF:

0.233

AC:

2004

ExAC

AF:

0.294

AC:

35743

Asia WGS

AF:

0.449

AC:

1559

AN:

3478

EpiCase

AF:

0.234

EpiControl

AF:

0.240

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.040

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.00013

.;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0060

LIST_S2

Benign

0.39

T;T;T

MetaRNN

Benign

0.000073

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.55

.;.;N

PhyloP100

0.95

PrimateAI

Benign

0.27

PROVEAN

Benign

0.39

N;N;N

REVEL

Benign

0.083

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.039

MPC

0.092

ClinPred

0.0015

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.065

gMVP

0.012

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over