Genetic Variant NM_001172779.2:c.745A>G (chr3-169800667-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001172779.2(LRRC34):c.745A>G(p.Ser249Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,524,046 control chromosomes in the GnomAD database, including 73,257 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.33 ( 8949 hom., cov: 32)

Exomes 𝑓: 0.29 ( 64308 hom. )

Consequence

LRRC34
NM_001172779.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.68

Publications

77 publications found

Variant links:

Genes affected

LRRC34 (HGNC:28408): (leucine rich repeat containing 34) Predicted to be involved in cell differentiation. Predicted to be located in cytoplasm and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

LRRC34 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=2.6204407E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC34	NM_001172779.2 link	c.745A>G	p.Ser249Gly	missense_variant	Exon 7 of 11	ENST00000446859.7	NP_001166250.1	Q8IZ02-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC34	ENST00000446859.7 link	c.745A>G	p.Ser249Gly	missense_variant	Exon 7 of 11	2	NM_001172779.2	ENSP00000414635.1		Q8IZ02-2

Frequencies

GnomAD3 genomes

AF:

0.330

AC:

50201

AN:

151916

Hom.:

8924

Cov.:

show subpopulations

Gnomad AFR

AF:

0.391

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.393

Gnomad ASJ

AF:

0.220

Gnomad EAS

AF:

0.685

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.274

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.337

GnomAD2 exomes

AF:

0.369

AC:

49029

AN:

132890

AF XY:

0.359

show subpopulations

Gnomad AFR exome

AF:

0.385

Gnomad AMR exome

AF:

0.536

Gnomad ASJ exome

AF:

0.225

Gnomad EAS exome

AF:

0.687

Gnomad FIN exome

AF:

0.275

Gnomad NFE exome

AF:

0.264

Gnomad OTH exome

AF:

0.341

GnomAD4 exome

AF:

0.292

AC:

400521

AN:

1372012

Hom.:

64308

Cov.:

AF XY:

0.294

AC XY:

199537

AN XY:

677604

show subpopulations

African (AFR)

AF:

0.383

AC:

11981

AN:

31298

American (AMR)

AF:

0.518

AC:

18275

AN:

35260

Ashkenazi Jewish (ASJ)

AF:

0.233

AC:

5837

AN:

25088

East Asian (EAS)

AF:

0.713

AC:

25331

AN:

35516

South Asian (SAS)

AF:

0.365

AC:

28641

AN:

78410

European-Finnish (FIN)

AF:

0.286

AC:

9692

AN:

33860

Middle Eastern (MID)

AF:

0.337

AC:

1744

AN:

5178

European-Non Finnish (NFE)

AF:

0.263

AC:

281388

AN:

1070004

Other (OTH)

AF:

0.307

AC:

17632

AN:

57398

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

11668

23336

35003

46671

58339

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9776

19552

29328

39104

48880

<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:

0.331

AC:

50275

AN:

152034

Hom.:

8949

Cov.:

AF XY:

0.334

AC XY:

24857

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.391

AC:

16219

AN:

41452

American (AMR)

AF:

0.393

AC:

6001

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.220

AC:

764

AN:

3472

East Asian (EAS)

AF:

0.685

AC:

3542

AN:

5172

South Asian (SAS)

AF:

0.363

AC:

1753

AN:

4828

European-Finnish (FIN)

AF:

0.274

AC:

2896

AN:

10562

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.266

AC:

18073

AN:

67958

Other (OTH)

AF:

0.340

AC:

718

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1650

3299

4949

6598

8248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

506

1012

1518

2024

2530

<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:

0.294

Hom.:

26576

Bravo

AF:

0.349

TwinsUK

AF:

0.249

AC:

925

ALSPAC

AF:

0.269

AC:

1036

ExAC

AF:

0.304

AC:

4538

Asia WGS

AF:

0.512

AC:

1776

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.0093

T;.

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.039

T;T

MetaRNN

Benign

0.0000026

T;T

MetaSVM

Benign

-0.98

PhyloP100

2.7

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.043

Sift

Benign

0.46

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.0010

.;B

Vest4

0.064

MPC

0.057

ClinPred

0.0021

GERP RS

3.4

Varity_R

0.11

gMVP

0.43

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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