ENST00000392000.4:c.2347C>G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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]

ACMG classification

Verdict is Benign. Variant got -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

GnomAD3 exomes AF: 0.294 AC: 73913 AN: 251226 Hom.: 11857 AF XY: 0.293 AC XY: 39830 AN XY: 135796

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 SAS exome AF: 0.366

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

Gnomad4 AFR exome AF: 0.367

Gnomad4 AMR exome AF: 0.305

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.555

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.270

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.268

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

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.264

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
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

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