9-12775821-A-G

Variant names:

• chr9-12775821-A-G
• rs1819165512
• NM_203403.2:c.106A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_203403.2(LURAP1L):​c.106A>G​(p.Arg36Gly) 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. 15/20 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LURAP1L NM_203403.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.476
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059924453).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203403.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LURAP1L	NM_203403.2	MANE Select	c.106A>G	p.Arg36Gly	missense	Exon 1 of 2	NP_981948.1	Q8IV03
	LURAP1L-AS1	NR_125775.1		n.243+14799T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LURAP1L	ENST00000319264.4	TSL:1 MANE Select	c.106A>G	p.Arg36Gly	missense	Exon 1 of 2	ENSP00000321026.3	Q8IV03
	LURAP1L	ENST00000489107.1	TSL:2	n.154A>G		non_coding_transcript_exon	Exon 1 of 2
	LURAP1L-AS1	ENST00000417638.1	TSL:3	n.199+14799T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1453024 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 722744

African (AFR) AF: 0.00 AC: 0 AN: 32964

American (AMR) AF: 0.00 AC: 0 AN: 41766

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25850

East Asian (EAS) AF: 0.00 AC: 0 AN: 39560

South Asian (SAS) AF: 0.00 AC: 0 AN: 85666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108942

Other (OTH) AF: 0.00 AC: 0 AN: 59968

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.58
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.063	N
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.48
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.041
Sift	Benign	0.19	T
Sift4G	Benign	0.096	T
Vest4		0.062
MutPred		0.18		Gain of relative solvent accessibility (P = 0.0275)
MVP		0.16
MPC		0.036
ClinPred		0.020	T
GERP RS		-1.5
gMVP		0.14
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1819165512; hg19: chr9-12775820;