dbSNP rs149563961: LRRC27:p.Pro181Arg (chr10-132344639-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_030626.3(LRRC27):c.542C>G(p.Pro181Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,613,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

LRRC27
NM_030626.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.235

Publications

1 publications found

Variant links:

Genes affected

LRRC27 (HGNC:29346): (leucine rich repeat containing 27)

LRRC27 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02126795).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030626.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC27	NM_030626.3	MANE Select	c.542C>G	p.Pro181Arg	missense	Exon 5 of 11	NP_085129.1	Q9C0I9-1
LRRC27	NM_001143757.2		c.542C>G	p.Pro181Arg	missense	Exon 5 of 11	NP_001137229.1	Q9C0I9-1
LRRC27	NM_001143758.2		c.542C>G	p.Pro181Arg	missense	Exon 5 of 8	NP_001137230.1	Q9C0I9-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC27	ENST00000368614.8	TSL:1 MANE Select	c.542C>G	p.Pro181Arg	missense	Exon 5 of 11	ENSP00000357603.3	Q9C0I9-1
LRRC27	ENST00000368613.8	TSL:1	c.542C>G	p.Pro181Arg	missense	Exon 5 of 11	ENSP00000357602.4	Q9C0I9-1
LRRC27	ENST00000625755.2	TSL:1	c.542C>G	p.Pro181Arg	missense	Exon 5 of 8	ENSP00000486582.1	Q9C0I9-4

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

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

GnomAD2 exomes

AF:

0.0000875

AC:

AN:

251328

AF XY:

0.0000515

show subpopulations

Gnomad AFR exome

AF:

0.000861

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000239

AC:

AN:

1461518

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727034

show subpopulations

African (AFR)

AF:

0.000568

AC:

AN:

33474

American (AMR)

AF:

0.000179

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111748

Other (OTH)

AF:

0.0000828

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000204

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.000746

AC:

AN:

41550

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000756

Hom.:

Bravo

AF:

0.000276

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.81

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.037

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.69

M_CAP

Benign

0.0032

MetaRNN

Benign

0.021

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

-0.23

PrimateAI

Benign

0.20

PROVEAN

Benign

-1.7

REVEL

Benign

0.041

Sift

Benign

0.086

Sift4G

Benign

0.45

Polyphen

0.91

Vest4

0.20

MVP

0.16

MPC

0.39

ClinPred

0.029

GERP RS

-3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.036

gMVP

0.31

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over