NM_181506.5:c.155C>T

Variant names:

• chr5-62579593-C-T
• rs1408227447
• NM_181506.5:c.155C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_181506.5(LRRC70):​c.155C>T​(p.Ser52Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000774 in 1,550,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: LRRC70 NM_181506.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16536397).
• BS2: High AC in GnomAdExome4 at 10 AD gene.

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.155C>T	p.Ser52Leu	missense	Exon 2 of 2	NP_852607.3
	IPO11	NM_016338.5	MANE Select	c.2583-11984C>T		intron	N/A	NP_057422.3
	IPO11	NM_001134779.2		c.2703-11984C>T		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.155C>T	p.Ser52Leu	missense	Exon 2 of 2	ENSP00000399441.1	Q7Z2Q7
	IPO11	ENST00000325324.11	TSL:1 MANE Select	c.2583-11984C>T		intron	N/A	ENSP00000316651.6	Q9UI26-1
	IPO11	ENST00000424533.5	TSL:2	n.*73+110C>T		intron	N/A	ENSP00000395685.1	F8WDV0

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152008 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000195 AC: 3 AN: 153550 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000811

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000715 AC: 10 AN: 1398888 Hom.: 0 Cov.: 32 AF XY: 0.0000116 AC XY: 8 AN XY: 689964

African (AFR) AF: 0.00 AC: 0 AN: 31572

American (AMR) AF: 0.000112 AC: 4 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25146

East Asian (EAS) AF: 0.00 AC: 0 AN: 35706

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00000371 AC: 4 AN: 1078612

Other (OTH) AF: 0.0000173 AC: 1 AN: 57968

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152008 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74226

African (AFR) AF: 0.0000241 AC: 1 AN: 41416

American (AMR) AF: 0.0000657 AC: 1 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67976

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000491

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	0.10
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Benign	0.095
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.3
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.077
Sift	Benign	0.39	T
Sift4G	Uncertain	0.015	D
Polyphen		0.96	D
Vest4		0.15
MutPred		0.41		Loss of disorder (P = 0.0405)
MVP		0.25
ClinPred		0.45	T
GERP RS		4.5
Varity_R		0.10
gMVP		0.33
Mutation Taster		=99/1	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: rs1408227447; hg19: chr5-61875420;