Genetic Variant NM_181506.5:c.111G>C (chr5-62579549-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_181506.5(LRRC70):c.111G>C(p.Gln37His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000451 in 1,551,080 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: 0.0000036 ( 0 hom. )

Consequence

LRRC70
NM_181506.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.17

Publications

0 publications found

Variant links:

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]

LRRC70 links:

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 links:

IPO11-LRRC70 (HGNC:):

IPO11-LRRC70 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04527062).

BS2

High AC in GnomAdExome4 at 5 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC70	NM_181506.5	MANE Select	c.111G>C	p.Gln37His	missense	Exon 2 of 2	NP_852607.3
IPO11	NM_016338.5	MANE Select	c.2583-12028G>C		intron	N/A	NP_057422.3
IPO11	NM_001134779.2		c.2703-12028G>C		intron	N/A	NP_001128251.1	Q9UI26-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC70	ENST00000334994.6	TSL:1 MANE Select	c.111G>C	p.Gln37His	missense	Exon 2 of 2	ENSP00000399441.1	Q7Z2Q7
IPO11	ENST00000325324.11	TSL:1 MANE Select	c.2583-12028G>C		intron	N/A	ENSP00000316651.6	Q9UI26-1
IPO11	ENST00000424533.5	TSL:2	n.*73+66G>C		intron	N/A	ENSP00000395685.1	F8WDV0

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000325

AC:

AN:

153684

AF XY:

0.0000245

show subpopulations

Gnomad AFR exome

AF:

0.000506

Gnomad AMR exome

AF:

0.0000405

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:

0.00000357

AC:

AN:

1398896

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

689968

show subpopulations

African (AFR)

AF:

0.0000950

AC:

AN:

31566

American (AMR)

AF:

0.0000280

AC:

AN:

35698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25156

East Asian (EAS)

AF:

0.00

AC:

AN:

35710

South Asian (SAS)

AF:

0.00

AC:

AN:

79218

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49274

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1078608

Other (OTH)

AF:

0.00

AC:

AN:

57976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41556

American (AMR)

AF:

0.00

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67966

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000934

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0047

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.43

M_CAP

Benign

0.0044

MetaRNN

Benign

0.045

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.57

PhyloP100

1.2

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.78

REVEL

Benign

0.060

Sift

Uncertain

0.026

Sift4G

Uncertain

0.0090

Polyphen

0.0050

Vest4

0.17

MutPred

0.48

Loss of sheet (P = 0.1907)

MVP

0.048

ClinPred

0.022

GERP RS

0.55

Varity_R

0.062

gMVP

0.44

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over