Variant 7-150337493-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001142928.2(LRRC61):c.632G>A(p.Arg211Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000025 in 1,602,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

LRRC61
NM_001142928.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.307

Variant links:

Genes affected

LRRC61 (HGNC:21704): (leucine rich repeat containing 61) Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

LRRC61 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.041057736).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRRC61	NM_001142928.2 linkuse as main transcript	c.632G>A	p.Arg211Gln	missense_variant	3/3	ENST00000359623.9	NP_001136400.1
LRRC61	NM_001363433.1 linkuse as main transcript	c.632G>A	p.Arg211Gln	missense_variant	3/3		NP_001350362.1
LRRC61	NM_001363434.1 linkuse as main transcript	c.632G>A	p.Arg211Gln	missense_variant	3/3		NP_001350363.1
LRRC61	NM_023942.3 linkuse as main transcript	c.632G>A	p.Arg211Gln	missense_variant	2/2		NP_076431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LRRC61	ENST00000359623.9 linkuse as main transcript	c.632G>A	p.Arg211Gln	missense_variant	3/3	2	NM_001142928.2	ENSP00000352642	P1
LRRC61	ENST00000323078.7 linkuse as main transcript	c.632G>A	p.Arg211Gln	missense_variant	2/2	1		ENSP00000339047	P1
	ENST00000647589.1 linkuse as main transcript	n.11G>A		non_coding_transcript_exon_variant	1/2
LRRC61	ENST00000493307.1 linkuse as main transcript	c.632G>A	p.Arg211Gln	missense_variant	4/4	5		ENSP00000420560	P1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

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:

0.0000211

AC:

AN:

236810

Hom.:

AF XY:

0.0000154

AC XY:

AN XY:

129562

show subpopulations

Gnomad AFR exome

AF:

0.0000655

Gnomad AMR exome

AF:

0.0000583

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000919

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000228

AC:

AN:

1450282

Hom.:

Cov.:

AF XY:

0.0000208

AC XY:

AN XY:

721752

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.000169

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

Bravo

AF:

0.0000907

ExAC

AF:

0.0000330

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

Feb 09, 2023

The c.632G>A (p.R211Q) alteration is located in exon 3 (coding exon 1) of the LRRC61 gene. This alteration results from a G to A substitution at nucleotide position 632, causing the arginine (R) at amino acid position 211 to be replaced by a glutamine (Q). 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

0.077

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.00041

T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.59

.;.;T

M_CAP

Benign

0.0069

MetaRNN

Benign

0.041

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L;L

MutationTaster

Benign

0.85

D;D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.31

N;N;N

REVEL

Benign

0.033

Sift

Benign

0.35

T;T;T

Sift4G

Benign

0.42

T;T;T

Polyphen

0.047

B;B;B

Vest4

0.13

MVP

0.15

MPC

0.23

ClinPred

0.014

GERP RS

2.0

Varity_R

0.025

gMVP

0.20

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