chr5-62579549-G-C

Position:

chr5-62579549-G-C

Variant summary

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

The ENST00000334994.6(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. 13/20 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
ENST00000334994.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.17

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=0.04527062).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC70	NM_181506.5 linkuse as main transcript	c.111G>C	p.Gln37His	missense_variant	2/2	ENST00000334994.6	NP_852607.3	Q7Z2Q7
IPO11	NM_016338.5 linkuse as main transcript	c.2583-12028G>C		intron_variant		ENST00000325324.11	NP_057422.3	Q9UI26-1
IPO11	NM_001134779.2 linkuse as main transcript	c.2703-12028G>C		intron_variant			NP_001128251.1	Q9UI26-2
IPO11-LRRC70	NR_073584.1 linkuse as main transcript	n.201+614G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LRRC70	ENST00000334994.6 linkuse as main transcript	c.111G>C	p.Gln37His	missense_variant	2/2	1	NM_181506.5	ENSP00000399441.1	Q7Z2Q7
IPO11	ENST00000325324.11 linkuse as main transcript	c.2583-12028G>C		intron_variant		1	NM_016338.5	ENSP00000316651.6	Q9UI26-1
IPO11	ENST00000424533.5 linkuse as main transcript	n.*73+66G>C		intron_variant		2		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

GnomAD3 exomes

AF:

0.0000325

AC:

AN:

153684

Hom.:

AF XY:

0.0000245

AC XY:

AN XY:

81538

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 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:

0.00000357

AC:

AN:

1398896

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

689968

show subpopulations

Gnomad4 AFR exome

AF:

0.0000950

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.27e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000934

AC:

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

Dec 26, 2023

The c.111G>C (p.Q37H) alteration is located in exon 2 (coding exon 1) of the LRRC70 gene. This alteration results from a G to C substitution at nucleotide position 111, causing the glutamine (Q) at amino acid position 37 to be replaced by a histidine (H). 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

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0047

T;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.43

T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.045

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.57

N;.

MutationTaster

Benign

1.0

D;D;D;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.78

N;D

REVEL

Benign

0.060

Sift

Uncertain

0.026

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.0050

B;.

Vest4

0.17

MutPred

0.48

Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);

MVP

0.048

ClinPred

0.022

GERP RS

0.55

Varity_R

0.062

gMVP

0.44

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