1-110948007-C-G

Position:

• chr1-110948007-C-G

Variant summary

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

The NM_018372.4(LRIF1):​c.2262G>C​(p.Glu754Asp) 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. 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: -0.00200

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24789673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRIF1	NM_018372.4	c.2262G>C	p.Glu754Asp	missense_variant	4/4	ENST00000369763.5
LRIF1	NM_001006945.2	c.654G>C	p.Glu218Asp	missense_variant	3/3
LRIF1	XM_005271029.5	c.2259G>C	p.Glu753Asp	missense_variant	4/4
LRIF1	XM_017001769.3	c.1869+1844G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRIF1	ENST00000369763.5	c.2262G>C	p.Glu754Asp	missense_variant	4/4	5	NM_018372.4	P1
	ENST00000440689.1	n.1694+2847C>G		intron_variant, non_coding_transcript_variant		2
LRIF1	ENST00000485275.2	c.654G>C	p.Glu218Asp	missense_variant	3/3	2
LRIF1	ENST00000494675.5	c.654G>C	p.Glu218Asp	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

Feb 10, 2023

The c.2262G>C (p.E754D) alteration is located in exon 4 (coding exon 4) of the LRIF1 gene. This alteration results from a G to C substitution at nucleotide position 2262, causing the glutamic acid (E) at amino acid position 754 to be replaced by an aspartic acid (D). 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	0.56
BayesDel_addAF	Benign	0.0025	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;.;.
Eigen	Benign	0.18
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.83	T;.;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.7	M;.;.
MutationTaster	Benign	0.83	D;D;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.012	D;D;D
Sift4G	Uncertain	0.030	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.38
MutPred		0.12		Loss of ubiquitination at K755 (P = 0.1278);.;.;
MVP		0.64
MPC		0.30
ClinPred		0.98	D
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.061

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: chr1-111490629;