1-110947994-G-T

Position:

• chr1-110947994-G-T

Variant summary

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

The NM_018372.4(LRIF1):​c.2275C>A​(p.Leu759Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRIF1 NM_018372.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.90

Genes affected

LRIF1 (HGNC:30299): (ligand dependent nuclear receptor interacting factor 1) Predicted to enable retinoic acid receptor binding activity. Involved in dosage compensation by inactivation of X chromosome. Located in Barr body; centriolar satellite; and nucleoplasm. Colocalizes with chromosome, telomeric region. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRIF1	NM_018372.4	c.2275C>A	p.Leu759Ile	missense_variant	4/4	ENST00000369763.5
LRIF1	NM_001006945.2	c.667C>A	p.Leu223Ile	missense_variant	3/3
LRIF1	XM_005271029.5	c.2272C>A	p.Leu758Ile	missense_variant	4/4
LRIF1	XM_017001769.3	c.1869+1857C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRIF1	ENST00000369763.5	c.2275C>A	p.Leu759Ile	missense_variant	4/4	5	NM_018372.4	P1
	ENST00000440689.1	n.1694+2834G>T		intron_variant, non_coding_transcript_variant		2
LRIF1	ENST00000485275.2	c.667C>A	p.Leu223Ile	missense_variant	3/3	2
LRIF1	ENST00000494675.5	c.667C>A	p.Leu223Ile	missense_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

May 04, 2022

The c.2275C>A (p.L759I) alteration is located in exon 4 (coding exon 4) of the LRIF1 gene. This alteration results from a C to A substitution at nucleotide position 2275, causing the leucine (L) at amino acid position 759 to be replaced by an isoleucine (I). 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	0.49
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;.;.
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.83	T;.;T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.7	M;.;.
MutationTaster	Benign	0.68	D;D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.52
MutPred		0.33		Gain of methylation at K764 (P = 0.098);.;.;
MVP		0.83
MPC		0.32
ClinPred		0.97	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.58
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-111490616;