Variant 5-62580123-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000334994.6(LRRC70):c.685A>C(p.Ser229Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000122 in 1,551,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

LRRC70
ENST00000334994.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.63

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:

LRRC70 (HGNC:):

LRRC70 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.035386562).

BS2

High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC70	NM_181506.5 linkuse as main transcript	c.685A>C	p.Ser229Arg	missense_variant	2/2	ENST00000334994.6	NP_852607.3	Q7Z2Q7
IPO11	NM_016338.5 linkuse as main transcript	c.2583-11454A>C		intron_variant		ENST00000325324.11	NP_057422.3	Q9UI26-1
IPO11	NM_001134779.2 linkuse as main transcript	c.2703-11454A>C		intron_variant			NP_001128251.1	Q9UI26-2
IPO11-LRRC70	NR_073584.1 linkuse as main transcript	n.201+1188A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LRRC70	ENST00000334994.6 linkuse as main transcript	c.685A>C	p.Ser229Arg	missense_variant	2/2	1	NM_181506.5	ENSP00000399441.1	Q7Z2Q7
IPO11	ENST00000325324.11 linkuse as main transcript	c.2583-11454A>C		intron_variant		1	NM_016338.5	ENSP00000316651.6	Q9UI26-1
IPO11	ENST00000424533.5 linkuse as main transcript	n.*74-331A>C		intron_variant		2		ENSP00000395685.1	F8WDV0

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000769

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

GnomAD3 exomes

AF:

0.0000977

AC:

AN:

153460

Hom.:

AF XY:

0.0000859

AC XY:

AN XY:

81448

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00138

Gnomad SAS 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:

0.0000114

AC:

AN:

1398926

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

689984

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000392

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000345

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 10, 2023

The c.685A>C (p.S229R) alteration is located in exon 2 (coding exon 1) of the LRRC70 gene. This alteration results from a A to C substitution at nucleotide position 685, causing the serine (S) at amino acid position 229 to be replaced by an arginine (R). 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

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.019

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.32

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.24

M_CAP

Benign

0.014

MetaRNN

Benign

0.035

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.30

MutationTaster

Benign

0.99

D;D;D;D;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.7

REVEL

Benign

0.046

Sift

Benign

0.51

Sift4G

Benign

0.24

Polyphen

0.095

Vest4

0.19

MutPred

0.36

Gain of MoRF binding (P = 0.0173);

MVP

0.23

ClinPred

0.077

GERP RS

3.3

Varity_R

0.18

gMVP

0.87

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over