1-110951346-G-A

Position:

• chr1-110951346-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018372.4(LRIF1):​c.1538C>T​(p.Ser513Phe) variant causes a missense change. 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: 4.45

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]

ENSG00000232811 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40434074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRIF1	NM_018372.4	c.1538C>T	p.Ser513Phe	missense_variant	2/4	ENST00000369763.5	NP_060842.3
LRIF1	XM_005271029.5	c.1538C>T	p.Ser513Phe	missense_variant	2/4		XP_005271086.1
LRIF1	XM_017001769.3	c.1538C>T	p.Ser513Phe	missense_variant	2/4		XP_016857258.1
LRIF1	NM_001006945.2	c.-12-1223C>T		intron_variant			NP_001006946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRIF1	ENST00000369763.5	c.1538C>T	p.Ser513Phe	missense_variant	2/4	5	NM_018372.4	ENSP00000358778.4
LRIF1	ENST00000485275.2	c.-12-1223C>T		intron_variant		2		ENSP00000432290.1
LRIF1	ENST00000494675.5	c.-13+1186C>T		intron_variant		2		ENSP00000435259.1
ENSG00000232811	ENST00000440689.1	n.1695-838G>A		intron_variant		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

Jul 31, 2024

The c.1538C>T (p.S513F) alteration is located in exon 2 (coding exon 2) of the LRIF1 gene. This alteration results from a C to T substitution at nucleotide position 1538, causing the serine (S) at amino acid position 513 to be replaced by a phenylalanine (F). 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	Benign	0.25
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.17
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.041	D
Polyphen		1.0	D
Vest4		0.35
MutPred		0.48		Loss of disorder (P = 0.0072);
MVP		0.71
MPC		0.38
ClinPred		0.89	D
GERP RS		5.8
Varity_R		0.17
gMVP		0.31

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: chr1-111493968;