rs3213869

Positions:

• chr2-237760140-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001137550.2(LRRFIP1):​c.1394A>G​(p.Gln465Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0426 in 1,613,590 control chromosomes in the GnomAD database, including 1,617 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.

• Frequency:
  • Genomes: 𝑓 0.033 (104 hom., cov: 32)
  • Exomes 𝑓: 0.044 (1513 hom.)
• Consequence: LRRFIP1 NM_001137550.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360

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=0.0028757453).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.053 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRFIP1	NM_001137550.2	c.1394A>G	p.Gln465Arg	missense_variant	19/24	ENST00000308482.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRFIP1	ENST00000308482.14	c.1394A>G	p.Gln465Arg	missense_variant	19/24	1	NM_001137550.2	P1

Frequencies

GnomAD3 genomes AF: 0.0333 AC: 5062 AN: 152194 Hom.: 104 Cov.: 32

Gnomad AFR AF: 0.00922

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0326

Gnomad ASJ AF: 0.0427

Gnomad EAS AF: 0.0587

Gnomad SAS AF: 0.0387

Gnomad FIN AF: 0.0276

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0454

Gnomad OTH AF: 0.0441

GnomAD3 exomes AF: 0.0389 AC: 9768 AN: 251368 Hom.: 240 AF XY: 0.0402 AC XY: 5460 AN XY: 135866

Gnomad AFR exome AF: 0.00947

Gnomad AMR exome AF: 0.0220

Gnomad ASJ exome AF: 0.0430

Gnomad EAS exome AF: 0.0621

Gnomad SAS exome AF: 0.0409

Gnomad FIN exome AF: 0.0283

Gnomad NFE exome AF: 0.0453

Gnomad OTH exome AF: 0.0421

GnomAD4 exome AF: 0.0436 AC: 63651 AN: 1461278 Hom.: 1513 Cov.: 31 AF XY: 0.0436 AC XY: 31732 AN XY: 726972

Gnomad4 AFR exome AF: 0.00756

Gnomad4 AMR exome AF: 0.0231

Gnomad4 ASJ exome AF: 0.0437

Gnomad4 EAS exome AF: 0.0475

Gnomad4 SAS exome AF: 0.0396

Gnomad4 FIN exome AF: 0.0278

Gnomad4 NFE exome AF: 0.0463

Gnomad4 OTH exome AF: 0.0434

GnomAD4 genome AF: 0.0332 AC: 5059 AN: 152312 Hom.: 104 Cov.: 32 AF XY: 0.0328 AC XY: 2445 AN XY: 74484

Gnomad4 AFR AF: 0.00919

Gnomad4 AMR AF: 0.0325

Gnomad4 ASJ AF: 0.0427

Gnomad4 EAS AF: 0.0584

Gnomad4 SAS AF: 0.0383

Gnomad4 FIN AF: 0.0276

Gnomad4 NFE AF: 0.0454

Gnomad4 OTH AF: 0.0436

Alfa AF: 0.0452 Hom.: 396

Bravo AF: 0.0318

TwinsUK AF: 0.0467 AC: 173

ALSPAC AF: 0.0483 AC: 186

ESP6500AA AF: 0.0141 AC: 62

ESP6500EA AF: 0.0449 AC: 386

ExAC AF: 0.0387 AC: 4705

Asia WGS AF: 0.0440 AC: 153 AN: 3478

EpiCase AF: 0.0473

EpiControl AF: 0.0538

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.40
DANN	Benign	0.67
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.75	T;T;T;T
MetaRNN	Benign	0.0029	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Benign	0.082
Sift	Benign	0.52	T;T;T;T
Sift4G	Benign	0.54	T;T;T;T
Polyphen		0.98, 0.94	.;D;D;P
Vest4		0.037
MPC		0.078
ClinPred		0.023	T
GERP RS		-9.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.067
gMVP		0.034

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: rs3213869; hg19: chr2-238668783; COSMIC: COSV55250153; COSMIC: COSV55250153;