2-237760140-A-G

Variant names:

• chr2-237760140-A-G
• rs3213869
• NM_001137550.2:c.1394A>G

Variant summary

Our verdict is Benign. The variant received -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. 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 (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
• Publications: 18 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=0.0028757453).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.053 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001137550.2. 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.1394A>G	p.Gln465Arg	missense	Exon 19 of 24	NP_001131022.1	Q32MZ4-4
	LRRFIP1	NM_001137552.2		c.824A>G	p.Gln275Arg	missense	Exon 10 of 11	NP_001131024.1	Q32MZ4-1
	LRRFIP1	NM_004735.4		c.752A>G	p.Gln251Arg	missense	Exon 9 of 10	NP_004726.2	Q32MZ4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRFIP1	ENST00000308482.14	TSL:1 MANE Select	c.1394A>G	p.Gln465Arg	missense	Exon 19 of 24	ENSP00000310109.9	Q32MZ4-4
	LRRFIP1	ENST00000392000.4	TSL:1	c.824A>G	p.Gln275Arg	missense	Exon 10 of 11	ENSP00000375857.4	Q32MZ4-1
	LRRFIP1	ENST00000244815.9	TSL:1	c.752A>G	p.Gln251Arg	missense	Exon 9 of 10	ENSP00000244815.5	Q32MZ4-2

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

GnomAD2 exomes AF: 0.0389 AC: 9768 AN: 251368 AF XY: 0.0402

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 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

African (AFR) AF: 0.00756 AC: 253 AN: 33462

American (AMR) AF: 0.0231 AC: 1034 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.0437 AC: 1143 AN: 26126

East Asian (EAS) AF: 0.0475 AC: 1887 AN: 39692

South Asian (SAS) AF: 0.0396 AC: 3416 AN: 86206

European-Finnish (FIN) AF: 0.0278 AC: 1484 AN: 53402

Middle Eastern (MID) AF: 0.0667 AC: 385 AN: 5768

European-Non Finnish (NFE) AF: 0.0463 AC: 51428 AN: 1111540

Other (OTH) AF: 0.0434 AC: 2621 AN: 60378

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

African (AFR) AF: 0.00919 AC: 382 AN: 41574

American (AMR) AF: 0.0325 AC: 498 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0427 AC: 148 AN: 3468

East Asian (EAS) AF: 0.0584 AC: 303 AN: 5188

South Asian (SAS) AF: 0.0383 AC: 185 AN: 4832

European-Finnish (FIN) AF: 0.0276 AC: 293 AN: 10608

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0454 AC: 3090 AN: 68024

Other (OTH) AF: 0.0436 AC: 92 AN: 2110

Alfa AF: 0.0432 Hom.: 660

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 v4.9

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
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.35	N
PhyloP100		-0.36
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.082
Sift	Benign	0.52	T
Sift4G	Benign	0.54	T
Polyphen		0.98	D
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
Mutation Taster		=99/1	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: rs3213869; hg19: chr2-238668783; COSMIC: COSV55250153; COSMIC: COSV55250153;