dbSNP rs6512265: LRRC25:p.Pro294Ser (chr19-18392025-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_145256.3(LRRC25):c.880C>T(p.Pro294Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 1,613,584 control chromosomes in the GnomAD database, including 369,314 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.72 ( 39954 hom., cov: 31)

Exomes 𝑓: 0.67 ( 329360 hom. )

Consequence

LRRC25
NM_145256.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.482

Publications

53 publications found

Variant links:

Genes affected

LRRC25 (HGNC:29806): (leucine rich repeat containing 25) Predicted to be located in cytoplasm. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC25 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.648493E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC25	NM_145256.3 link	c.880C>T	p.Pro294Ser	missense_variant	Exon 2 of 2	ENST00000339007.4	NP_660299.2	Q8N386
LRRC25	XM_005259739.5 link	c.880C>T	p.Pro294Ser	missense_variant	Exon 3 of 3		XP_005259796.1	Q8N386

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC25	ENST00000339007.4 link	c.880C>T	p.Pro294Ser	missense_variant	Exon 2 of 2	1	NM_145256.3	ENSP00000340983.2		Q8N386
LRRC25	ENST00000595840.1 link	c.880C>T	p.Pro294Ser	missense_variant	Exon 3 of 3	1		ENSP00000472290.1		Q8N386

Frequencies

GnomAD3 genomes

AF:

0.721

AC:

109515

AN:

151908

Hom.:

39912

Cov.:

show subpopulations

Gnomad AFR

AF:

0.821

Gnomad AMI

AF:

0.662

Gnomad AMR

AF:

0.695

Gnomad ASJ

AF:

0.703

Gnomad EAS

AF:

0.652

Gnomad SAS

AF:

0.626

Gnomad FIN

AF:

0.810

Gnomad MID

AF:

0.671

Gnomad NFE

AF:

0.667

Gnomad OTH

AF:

0.668

GnomAD2 exomes

AF:

0.693

AC:

174049

AN:

251114

AF XY:

0.686

show subpopulations

Gnomad AFR exome

AF:

0.831

Gnomad AMR exome

AF:

0.717

Gnomad ASJ exome

AF:

0.684

Gnomad EAS exome

AF:

0.653

Gnomad FIN exome

AF:

0.795

Gnomad NFE exome

AF:

0.671

Gnomad OTH exome

AF:

0.665

GnomAD4 exome

AF:

0.670

AC:

979326

AN:

1461558

Hom.:

329360

Cov.:

AF XY:

0.668

AC XY:

485428

AN XY:

727096

show subpopulations

African (AFR)

AF:

0.825

AC:

27617

AN:

33478

American (AMR)

AF:

0.716

AC:

32017

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.687

AC:

17941

AN:

26132

East Asian (EAS)

AF:

0.609

AC:

24163

AN:

39684

South Asian (SAS)

AF:

0.636

AC:

54841

AN:

86246

European-Finnish (FIN)

AF:

0.791

AC:

42235

AN:

53402

Middle Eastern (MID)

AF:

0.620

AC:

3573

AN:

5766

European-Non Finnish (NFE)

AF:

0.662

AC:

736294

AN:

1111758

Other (OTH)

AF:

0.673

AC:

40645

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

17021

34041

51062

68082

85103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19210

38420

57630

76840

96050

<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:

0.721

AC:

109614

AN:

152026

Hom.:

39954

Cov.:

AF XY:

0.724

AC XY:

53804

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.821

AC:

34073

AN:

41484

American (AMR)

AF:

0.695

AC:

10599

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.703

AC:

2435

AN:

3466

East Asian (EAS)

AF:

0.652

AC:

3367

AN:

5162

South Asian (SAS)

AF:

0.627

AC:

3021

AN:

4822

European-Finnish (FIN)

AF:

0.810

AC:

8582

AN:

10594

Middle Eastern (MID)

AF:

0.673

AC:

198

AN:

294

European-Non Finnish (NFE)

AF:

0.667

AC:

45336

AN:

67938

Other (OTH)

AF:

0.664

AC:

1399

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1527

3055

4582

6110

7637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

830

1660

2490

3320

4150

<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:

0.679

Hom.:

136114

Bravo

AF:

0.718

TwinsUK

AF:

0.667

AC:

2475

ALSPAC

AF:

0.665

AC:

2562

ESP6500AA

AF:

0.835

AC:

3679

ESP6500EA

AF:

0.659

AC:

5668

ExAC

AF:

0.691

AC:

83914

Asia WGS

AF:

0.659

AC:

2294

AN:

3478

EpiCase

AF:

0.652

EpiControl

AF:

0.654

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.9

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.14

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.44

.;T

MetaRNN

Benign

8.6e-7

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L

PhyloP100

-0.48

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.4

D;.

REVEL

Benign

0.013

Sift

Benign

0.070

T;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.027

B;B

Vest4

0.019

MPC

0.46

ClinPred

0.0098

GERP RS

-1.6

Varity_R

0.043

gMVP

0.41

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over