rs146092308

Variant names:

• chr5-62579937-C-A
• rs146092308
• NM_181506.5:c.499C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-62579937-C-A
• chr5-62579937-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181506.5(LRRC70):​c.499C>A​(p.Arg167Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R167C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: LRRC70 NM_181506.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.254
• Publications: 0 publications found

Genes affected

LRRC70 (HGNC:35155): (leucine rich repeat containing 70) Involved in positive regulation of response to cytokine stimulus. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

IPO11 (HGNC:20628): (importin 11) Importins, including IPO11, are a members of the karyopherin/importin-beta family of transport receptors (see KPNB1; 602738) that mediate nucleocytoplasmic transport of protein and RNA cargoes (Plafker and Macara, 2000 [PubMed 11032817]).[supplied by OMIM, Sep 2008]

IPO11-LRRC70 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09481689).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181506.5. 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
	LRRC70	NM_181506.5	MANE Select	c.499C>A	p.Arg167Ser	missense	Exon 2 of 2	NP_852607.3
	IPO11	NM_016338.5	MANE Select	c.2583-11640C>A		intron	N/A	NP_057422.3
	IPO11	NM_001134779.2		c.2703-11640C>A		intron	N/A	NP_001128251.1	Q9UI26-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC70	ENST00000334994.6	TSL:1 MANE Select	c.499C>A	p.Arg167Ser	missense	Exon 2 of 2	ENSP00000399441.1	Q7Z2Q7
	IPO11	ENST00000325324.11	TSL:1 MANE Select	c.2583-11640C>A		intron	N/A	ENSP00000316651.6	Q9UI26-1
	IPO11	ENST00000424533.5	TSL:2	n.*73+454C>A		intron	N/A	ENSP00000395685.1	F8WDV0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399046 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 690056

African (AFR) AF: 0.0000317 AC: 1 AN: 31572

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25166

East Asian (EAS) AF: 0.00 AC: 0 AN: 35702

South Asian (SAS) AF: 0.00 AC: 0 AN: 79226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078744

Other (OTH) AF: 0.00 AC: 0 AN: 57970

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	0.25
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	6.8
DANN	Benign	0.90
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.060	N
PhyloP100		-0.25
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.056
Sift	Benign	0.22	T
Sift4G	Benign	0.36	T
Polyphen		0.18	B
Vest4		0.34
MutPred		0.49		Loss of stability (P = 0.0839)
MVP		0.085
ClinPred		0.11	T
GERP RS		-0.20
Varity_R		0.15
gMVP		0.78
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs146092308; hg19: chr5-61875764;