9-12775922-G-C

Variant names:

• chr9-12775922-G-C
• NM_203403.2:c.207G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_203403.2(LURAP1L):​c.207G>C​(p.Leu69Phe) 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. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LURAP1L NM_203403.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.344

Genes affected

LURAP1L (HGNC:31452): (leucine rich adaptor protein 1 like) Predicted to be involved in positive regulation of I-kappaB kinase/NF-kappaB signaling. [provided by Alliance of Genome Resources, Apr 2022]

LURAP1L-AS1 (HGNC:49761): (LURAP1L antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057905287).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LURAP1L	NM_203403.2	c.207G>C	p.Leu69Phe	missense_variant	Exon 1 of 2	ENST00000319264.4	NP_981948.1
LURAP1L	XM_005251443.4	c.207G>C	p.Leu69Phe	missense_variant	Exon 1 of 2		XP_005251500.1
LURAP1L-AS1	NR_125775.1	n.243+14698C>G		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LURAP1L	ENST00000319264.4	c.207G>C	p.Leu69Phe	missense_variant	Exon 1 of 2	1	NM_203403.2	ENSP00000321026.3
LURAP1L	ENST00000489107.1	n.255G>C		non_coding_transcript_exon_variant	Exon 1 of 2	2
LURAP1L-AS1	ENST00000417638.1	n.199+14698C>G		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 12, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.207G>C (p.L69F) alteration is located in exon 1 (coding exon 1) of the LURAP1L gene. This alteration results from a G to C substitution at nucleotide position 207, causing the leucine (L) at amino acid position 69 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
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Uncertain	0.99
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.16	N
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.060
Sift	Benign	0.25	T
Sift4G	Benign	0.37	T
Vest4		0.15
MVP		0.33
MPC		0.042
ClinPred		0.11	T
GERP RS		0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.090

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: chr9-12775921;