2-237760140-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001137550.2(LRRFIP1):​c.1394A>T​(p.Gln465Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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: not found (cov: 32)
• Consequence: LRRFIP1 NM_001137550.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.067118466).

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>T	p.Gln465Leu	missense	Exon 19 of 24	NP_001131022.1	Q32MZ4-4
	LRRFIP1	NM_001137552.2		c.824A>T	p.Gln275Leu	missense	Exon 10 of 11	NP_001131024.1	Q32MZ4-1
	LRRFIP1	NM_004735.4		c.752A>T	p.Gln251Leu	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>T	p.Gln465Leu	missense	Exon 19 of 24	ENSP00000310109.9	Q32MZ4-4
	LRRFIP1	ENST00000392000.4	TSL:1	c.824A>T	p.Gln275Leu	missense	Exon 10 of 11	ENSP00000375857.4	Q32MZ4-1
	LRRFIP1	ENST00000244815.9	TSL:1	c.752A>T	p.Gln251Leu	missense	Exon 9 of 10	ENSP00000244815.5	Q32MZ4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.1
DANN	Benign	0.75
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.23	N
PhyloP100		-0.36
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.045
Sift	Benign	0.30	T
Sift4G	Benign	0.31	T
Polyphen		0.056	B
Vest4		0.059
MutPred		0.65		Gain of stability (P = 0.0061)
MVP		0.16
MPC		0.075
ClinPred		0.043	T
GERP RS		-9.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.082
gMVP		0.066
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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;