ENST00000392000.4:c.2347C>A

Variant names:

• chr2-237764060-C-A
• rs3739038
• ENST00000392000.4:c.2347C>A
• LRRFIP1 p.His783Asn

Variant summary

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

The ENST00000392000.4(LRRFIP1):​c.2347C>A​(p.His783Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LRRFIP1 ENST00000392000.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.953
• Publications: 36 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=0.04479167).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000392000.4. 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.1459+3855C>A		intron	N/A	NP_001131022.1	Q32MZ4-4
	LRRFIP1	NM_001137552.2		c.2347C>A	p.His783Asn	missense	Exon 11 of 11	NP_001131024.1	Q32MZ4-1
	LRRFIP1	NM_004735.4		c.2275C>A	p.His759Asn	missense	Exon 10 of 10	NP_004726.2	Q32MZ4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRFIP1	ENST00000392000.4	TSL:1	c.2347C>A	p.His783Asn	missense	Exon 11 of 11	ENSP00000375857.4	Q32MZ4-1
	LRRFIP1	ENST00000244815.9	TSL:1	c.2275C>A	p.His759Asn	missense	Exon 10 of 10	ENSP00000244815.5	Q32MZ4-2
	LRRFIP1	ENST00000289175.10	TSL:1	c.2179C>A	p.His727Asn	missense	Exon 8 of 8	ENSP00000289175.6	Q32MZ4-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461876 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 727238

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	11
DANN	Benign	0.36
DEOGEN2	Benign	0.00046	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.95
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.24	N
REVEL	Benign	0.085
Sift	Benign	0.16	T
Sift4G	Benign	0.58	T
Varity_R		0.060
gMVP		0.011
Mutation Taster		=97/3	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3739038;

hg19: chr2-238672703;