ENST00000392000.4:c.2069G>C

Variant names:

• chr2-237763782-G-C
• rs11680012
• ENST00000392000.4:c.2069G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000392000.4(LRRFIP1):​c.2069G>C​(p.Arg690Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0428 in 1,614,196 control chromosomes in the GnomAD database, including 1,618 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 0.033 (103 hom., cov: 32)
  • Exomes 𝑓: 0.044 (1515 hom.)
• Consequence: LRRFIP1 ENST00000392000.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.813
• Publications: 20 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002564013).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000392000.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRFIP1	NM_001137550.2	MANE Select	c.1459+3577G>C		intron	N/A	NP_001131022.1
	LRRFIP1	NM_001137552.2		c.2069G>C	p.Arg690Thr	missense	Exon 11 of 11	NP_001131024.1
	LRRFIP1	NM_004735.4		c.1997G>C	p.Arg666Thr	missense	Exon 10 of 10	NP_004726.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRFIP1	ENST00000392000.4	TSL:1	c.2069G>C	p.Arg690Thr	missense	Exon 11 of 11	ENSP00000375857.4
	LRRFIP1	ENST00000244815.9	TSL:1	c.1997G>C	p.Arg666Thr	missense	Exon 10 of 10	ENSP00000244815.5
	LRRFIP1	ENST00000289175.10	TSL:1	c.1901G>C	p.Arg634Thr	missense	Exon 8 of 8	ENSP00000289175.6

Frequencies

GnomAD3 genomes AF: 0.0332 AC: 5046 AN: 152212 Hom.: 103 Cov.: 32

Gnomad AFR AF: 0.00919

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0326

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.0583

Gnomad SAS AF: 0.0388

Gnomad FIN AF: 0.0277

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0453

Gnomad OTH AF: 0.0440

GnomAD2 exomes AF: 0.0389 AC: 9772 AN: 251000 AF XY: 0.0402

Gnomad AFR exome AF: 0.00949

Gnomad AMR exome AF: 0.0218

Gnomad ASJ exome AF: 0.0414

Gnomad EAS exome AF: 0.0625

Gnomad FIN exome AF: 0.0285

Gnomad NFE exome AF: 0.0455

Gnomad OTH exome AF: 0.0422

GnomAD4 exome AF: 0.0438 AC: 64042 AN: 1461866 Hom.: 1515 Cov.: 35 AF XY: 0.0439 AC XY: 31910 AN XY: 727232

African (AFR) AF: 0.00744 AC: 249 AN: 33480

American (AMR) AF: 0.0229 AC: 1023 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0423 AC: 1106 AN: 26136

East Asian (EAS) AF: 0.0478 AC: 1897 AN: 39700

South Asian (SAS) AF: 0.0398 AC: 3432 AN: 86256

European-Finnish (FIN) AF: 0.0280 AC: 1497 AN: 53412

Middle Eastern (MID) AF: 0.0662 AC: 382 AN: 5768

European-Non Finnish (NFE) AF: 0.0466 AC: 51846 AN: 1111996

Other (OTH) AF: 0.0432 AC: 2610 AN: 60396

GnomAD4 genome AF: 0.0331 AC: 5043 AN: 152330 Hom.: 103 Cov.: 32 AF XY: 0.0327 AC XY: 2438 AN XY: 74496

African (AFR) AF: 0.00916 AC: 381 AN: 41572

American (AMR) AF: 0.0325 AC: 498 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0415 AC: 144 AN: 3470

East Asian (EAS) AF: 0.0580 AC: 301 AN: 5188

South Asian (SAS) AF: 0.0384 AC: 185 AN: 4820

European-Finnish (FIN) AF: 0.0277 AC: 294 AN: 10620

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0453 AC: 3081 AN: 68034

Other (OTH) AF: 0.0435 AC: 92 AN: 2114

Alfa AF: 0.0429 Hom.: 56

Bravo AF: 0.0317

TwinsUK AF: 0.0469 AC: 174

ALSPAC AF: 0.0483 AC: 186

ESP6500AA AF: 0.0143 AC: 63

ESP6500EA AF: 0.0445 AC: 383

ExAC AF: 0.0387 AC: 4700

Asia WGS AF: 0.0440 AC: 153 AN: 3478

EpiCase AF: 0.0479

EpiControl AF: 0.0536

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.2
DANN	Benign	0.41
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.38	N
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.81
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.056
Sift	Benign	0.082	T
Sift4G	Benign	0.47	T
Polyphen		0.063	B
Vest4		0.10
MPC		0.12
ClinPred		0.00045	T
GERP RS		-0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.031
gMVP		0.024
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11680012; hg19: chr2-238672425; COSMIC: COSV55257383; COSMIC: COSV55257383;