rs3739038

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-237764060-C-A
• chr2-237764060-C-G
• chr2-237764060-C-T

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRFIP1	NM_001137550.2	c.1459+3855C>A		intron_variant	Intron 19 of 23	ENST00000308482.14	NP_001131022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRFIP1	ENST00000308482.14	c.1459+3855C>A		intron_variant	Intron 19 of 23	1	NM_001137550.2	ENSP00000310109.9

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 v4.3

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;T;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.045	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	.;.;N
PhyloP100		0.95
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.24	N;N;N
REVEL	Benign	0.085
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.58	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.093
MutPred		0.066		.;.;Gain of methylation at R779 (P = 0.148);
MVP		0.19
MPC		0.075
ClinPred		0.22	T
GERP RS		1.5
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

Other links and lift over

dbSNP: rs3739038; hg19: chr2-238672703;