Variant 1-70036125-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_001370785.2(LRRC7):c.2000C>G(p.Ser667Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000618 in 1,456,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

LRRC7
NM_001370785.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.13

Variant links:

Genes affected

LRRC7 (HGNC:18531): (leucine rich repeat containing 7) Predicted to be involved in several processes, including establishment or maintenance of epithelial cell apical/basal polarity; positive regulation of neuron projection development; and receptor clustering. Located in several cellular components, including centrosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LRRC7 links:

LRRC7-AS1 (HGNC:):

LRRC7-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant where missense usually causes diseases, LRRC7

BP4

Computational evidence support a benign effect (MetaRNN=0.21604744).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC7	NM_001370785.2 linkuse as main transcript	c.2000C>G	p.Ser667Cys	missense_variant	19/27	ENST00000651989.2
LRRC7-AS1	XR_001738107.2 linkuse as main transcript	n.3002G>C		non_coding_transcript_exon_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LRRC7	ENST00000651989.2 linkuse as main transcript	c.2000C>G	p.Ser667Cys	missense_variant	19/27		NM_001370785.2	P1
LRRC7	ENST00000415775.2 linkuse as main transcript	c.27-1988C>G		intron_variant		1
LRRC7	ENST00000310961.9 linkuse as main transcript	c.1901C>G	p.Ser634Cys	missense_variant	20/27	5
LRRC7	ENST00000651217.1 linkuse as main transcript	n.1916C>G		non_coding_transcript_exon_variant	17/25

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000162

AC:

AN:

246970

Hom.:

AF XY:

0.0000225

AC XY:

AN XY:

133452

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000338

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000268

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000618

AC:

AN:

1456400

Hom.:

Cov.:

AF XY:

0.00000828

AC XY:

AN XY:

724376

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000541

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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 17, 2023

The c.1886C>G (p.S629C) alteration is located in exon 17 (coding exon 17) of the LRRC7 gene. This alteration results from a C to G substitution at nucleotide position 1886, causing the serine (S) at amino acid position 629 to be replaced by a cysteine (C). 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

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

T;T

Eigen

Uncertain

0.60

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.90

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.17

Sift

Uncertain

0.0010

D;D

Polyphen

0.97

.;D

Vest4

0.49

MutPred

0.36

.;Loss of disorder (P = 0.037);

MVP

0.22

MPC

0.62

ClinPred

0.83

GERP RS

5.9

Varity_R

0.26

gMVP

0.49

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