Variant 17-46297471-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_014834.4(LRRC37A):c.2338G>C(p.Val780Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000060 ( 3 hom., cov: 18)

Exomes 𝑓: 0.00012 ( 40 hom. )

Failed GnomAD Quality Control

Consequence

LRRC37A
NM_014834.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.200

Variant links:

Genes affected

LRRC37A (HGNC:29069): (leucine rich repeat containing 37A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC37A links:

ARL17B (HGNC:32387): (ADP ribosylation factor like GTPase 17B) Predicted to enable GTP binding activity. Predicted to be involved in intracellular protein transport and vesicle-mediated transport. Predicted to be located in Golgi apparatus. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARL17B 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=0.0072587132).

BP6

Variant 17-46297471-G-C is Benign according to our data. Variant chr17-46297471-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3120581.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC37A	NM_014834.4 linkuse as main transcript	c.2338G>C	p.Val780Leu	missense_variant	1/14	ENST00000320254.5	NP_055649.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC37A	ENST00000320254.5 linkuse as main transcript	c.2338G>C	p.Val780Leu	missense_variant	1/14	1	NM_014834.4	ENSP00000326324	P2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

116400

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00671

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:

0.00129

AC:

AN:

50466

Hom.:

AF XY:

0.000943

AC XY:

AN XY:

25444

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0128

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000551

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000119

AC:

145

AN:

1220840

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

615498

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00543

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000108

Gnomad4 OTH exome

AF:

0.0000972

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000601

AC:

AN:

116486

Hom.:

Cov.:

AF XY:

0.0000725

AC XY:

AN XY:

55152

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00522

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.000102

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

1.4

DANN

Benign

0.81

DEOGEN2

Benign

0.0094

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0017

LIST_S2

Benign

0.55

T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.0073

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

.;M

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.039

Sift

Benign

0.13

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.0

.;B

Vest4

0.23

MutPred

0.27

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.068

ClinPred

0.036

GERP RS

-4.1

Varity_R

0.079

gMVP

0.049

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