rs3213869

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-237760140-A-C
• chr2-237760140-A-G
• chr2-237760140-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001137550.2(LRRFIP1):​c.1394A>C​(p.Gln465Pro) 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07431358).

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>C	p.Gln465Pro	missense	Exon 19 of 24	NP_001131022.1	Q32MZ4-4
	LRRFIP1	NM_001137552.2		c.824A>C	p.Gln275Pro	missense	Exon 10 of 11	NP_001131024.1	Q32MZ4-1
	LRRFIP1	NM_004735.4		c.752A>C	p.Gln251Pro	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>C	p.Gln465Pro	missense	Exon 19 of 24	ENSP00000310109.9	Q32MZ4-4
	LRRFIP1	ENST00000392000.4	TSL:1	c.824A>C	p.Gln275Pro	missense	Exon 10 of 11	ENSP00000375857.4	Q32MZ4-1
	LRRFIP1	ENST00000244815.9	TSL:1	c.752A>C	p.Gln251Pro	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	0.086
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.4
DANN	Benign	0.70
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.30	N
PhyloP100		-0.36
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.050
Sift	Benign	0.27	T
Sift4G	Benign	0.28	T
Polyphen		0.014	B
Vest4		0.12
MutPred		0.68		Loss of phosphorylation at Y274 (P = 0.0846)
MVP		0.16
MPC		0.088
ClinPred		0.068	T
GERP RS		-9.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.052
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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;