Variant 1-70023198-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001370785.2(LRRC7):c.1618G>A(p.Asp540Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000881 in 1,589,924 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000090 ( 2 hom. )

Consequence

LRRC7
NM_001370785.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.53

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:40843): (LRRC7 antisense RNA 1)

LRRC7-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08899796).

BS2

High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC7	NM_001370785.2 linkuse as main transcript	c.1618G>A	p.Asp540Asn	missense_variant	17/27	ENST00000651989.2
LRRC7-AS1	XR_001738107.2 linkuse as main transcript	n.4709-800C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC7	ENST00000651989.2 linkuse as main transcript	c.1618G>A	p.Asp540Asn	missense_variant	17/27		NM_001370785.2	P1
LRRC7-AS1	ENST00000414132.5 linkuse as main transcript	n.92-800C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152114

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:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000141

AC:

AN:

240806

Hom.:

AF XY:

0.000223

AC XY:

AN XY:

130160

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:

0.000969

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000547

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000904

AC:

130

AN:

1437810

Hom.:

Cov.:

AF XY:

0.000132

AC XY:

AN XY:

713568

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000786

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000210

Gnomad4 OTH exome

AF:

0.000101

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000151

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000181

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

Aug 12, 2021

The c.1504G>A (p.D502N) alteration is located in exon 15 (coding exon 15) of the LRRC7 gene. This alteration results from a G to A substitution at nucleotide position 1504, causing the aspartic acid (D) at amino acid position 502 to be replaced by an asparagine (N). 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

-0.47

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

T;T

Eigen

Benign

0.071

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.0052

MetaRNN

Benign

0.089

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;N

MutationTaster

Benign

0.69

D;D

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.57

N;N

REVEL

Benign

0.081

Sift

Uncertain

0.0050

D;D

Sift4G

Benign

0.084

.;T

Polyphen

0.55

.;P

Vest4

0.64

MVP

0.33

MPC

0.25

ClinPred

0.070

GERP RS

5.9

Varity_R

0.17

gMVP

0.38

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