2-237764060-C-G

Variant names:

• chr2-237764060-C-G
• rs3739038
• ENST00000392000.4:c.2347C>G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.953
• Publications: 36 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=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	c.1459+3855C>G		intron_variant	Intron 19 of 23	ENST00000308482.14	NP_001131022.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44271 AN: 151926 Hom.: 6799 Cov.: 32

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

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.: 36 AF XY: 0.260 AC XY: 188730 AN XY: 727220

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

GnomAD4 genome AF: 0.292 AC: 44330 AN: 152044 Hom.: 6816 Cov.: 32 AF XY: 0.300 AC XY: 22313 AN XY: 74328

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: 97 AN: 292

European-Non Finnish (NFE) AF: 0.234 AC: 15916 AN: 67964

Other (OTH) AF: 0.264 AC: 557 AN: 2108

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	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.46
DEOGEN2	Benign	0.00013	.;.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0060	N
LIST_S2	Benign	0.39	T;T;T
MetaRNN	Benign	0.000073	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.55	.;.;N
PhyloP100		0.95
PrimateAI	Benign	0.27	T
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	T
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)

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: rs3739038; hg19: chr2-238672703; COSMIC: COSV55257740; COSMIC: COSV55257740;