2-237692492-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000392000.4(LRRFIP1):c.37G>A(p.Asp13Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000058 in 1,380,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000058 (0 hom.)
• Consequence: LRRFIP1 ENST00000392000.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.19

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25377414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRFIP1	NM_001137550.2	c.97-16052G>A		intron_variant		ENST00000308482.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRFIP1	ENST00000308482.14	c.97-16052G>A		intron_variant		1	NM_001137550.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000580 AC: 8 AN: 1380422 Hom.: 0 Cov.: 32 AF XY: 0.00000734 AC XY: 5 AN XY: 680978

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000389

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000467

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2021

The c.37G>A (p.D13N) alteration is located in exon 1 (coding exon 1) of the LRRFIP1 gene. This alteration results from a G to A substitution at nucleotide position 37, causing the aspartic acid (D) at amino acid position 13 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	19
Dann	Uncertain	1.0
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.97	L;L;.;L
MutationTaster	Benign	0.65	D;D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Benign	0.093
Sift	Uncertain	0.0060	D;D;D;D
Sift4G	Uncertain	0.0050	D;D;T;D
Polyphen		1.0	D;D;.;D
Vest4		0.41
MutPred		0.14		Gain of MoRF binding (P = 0.0504);Gain of MoRF binding (P = 0.0504);Gain of MoRF binding (P = 0.0504);Gain of MoRF binding (P = 0.0504);
MVP		0.48
MPC		0.32
ClinPred		0.78	D
GERP RS		3.6
Varity_R		0.22
gMVP		0.18

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

Publications

LitVar

Other links and lift over

dbSNP: rs1318329206; hg19: chr2-238601135;