NM_022143.5:c.837T>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022143.5(LRRC4):c.837T>A(p.Ser279Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,613,560 control chromosomes in the GnomAD database, including 66,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8247 hom., cov: 32)

Exomes 𝑓: 0.28 ( 58274 hom. )

Consequence

LRRC4
NM_022143.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.655

Publications

24 publications found

Variant links:

Genes affected

LRRC4 (HGNC:15586): (leucine rich repeat containing 4) Predicted to be involved in modulation of chemical synaptic transmission and synapse organization. Predicted to act upstream of or within synapse organization. Predicted to be located in neuron spine and postsynaptic membrane. Predicted to be active in Schaffer collateral - CA1 synapse; glutamatergic synapse; and plasma membrane. Predicted to be integral component of postsynaptic density membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC4 links:

SND1 (HGNC:30646): (staphylococcal nuclease and tudor domain containing 1) This gene encodes a transcriptional co-activator that interacts with the acidic domain of Epstein-Barr virus nuclear antigen 2 (EBNA 2), a transcriptional activator that is required for B-lymphocyte transformation. Other transcription factors that interact with this protein are signal transducers and activators of transcription, STATs. This protein is also thought to be essential for normal cell growth. A similar protein in mammals and other organisms is a component of the RNA-induced silencing complex (RISC). [provided by RefSeq, Jul 2016]

SND1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 7-128029804-A-T is Benign according to our data. Variant chr7-128029804-A-T is described in ClinVar as Benign. ClinVar VariationId is 1258265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.655 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022143.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC4	NM_022143.5	MANE Select	c.837T>A	p.Ser279Ser	synonymous	Exon 2 of 2	NP_071426.1
	SND1	NM_014390.4	MANE Select	c.1779+38748A>T		intron	N/A	NP_055205.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LRRC4	ENST00000249363.4	TSL:1 MANE Select	c.837T>A	p.Ser279Ser	synonymous	Exon 2 of 2	ENSP00000249363.3
SND1	ENST00000354725.8	TSL:1 MANE Select	c.1779+38748A>T		intron	N/A	ENSP00000346762.3
SND1	ENST00000486037.1	TSL:3	c.426+38748A>T		intron	N/A	ENSP00000419327.1

Frequencies

GnomAD3 genomes

AF:

0.319

AC:

48400

AN:

151954

Hom.:

8223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.414

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.374

Gnomad ASJ

AF:

0.283

Gnomad EAS

AF:

0.200

Gnomad SAS

AF:

0.407

Gnomad FIN

AF:

0.267

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.264

Gnomad OTH

AF:

0.297

GnomAD2 exomes

AF:

0.309

AC:

77595

AN:

250930

AF XY:

0.304

show subpopulations

Gnomad AFR exome

AF:

0.418

Gnomad AMR exome

AF:

0.428

Gnomad ASJ exome

AF:

0.275

Gnomad EAS exome

AF:

0.211

Gnomad FIN exome

AF:

0.270

Gnomad NFE exome

AF:

0.266

Gnomad OTH exome

AF:

0.290

GnomAD4 exome

AF:

0.278

AC:

405782

AN:

1461488

Hom.:

58274

Cov.:

AF XY:

0.279

AC XY:

202484

AN XY:

727040

show subpopulations

African (AFR)

AF:

0.423

AC:

14148

AN:

33478

American (AMR)

AF:

0.426

AC:

19070

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

7297

AN:

26136

East Asian (EAS)

AF:

0.190

AC:

7559

AN:

39700

South Asian (SAS)

AF:

0.380

AC:

32740

AN:

86256

European-Finnish (FIN)

AF:

0.268

AC:

14204

AN:

53070

Middle Eastern (MID)

AF:

0.255

AC:

1468

AN:

5768

European-Non Finnish (NFE)

AF:

0.263

AC:

292516

AN:

1111966

Other (OTH)

AF:

0.278

AC:

16780

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

20297

40593

60890

81186

101483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10092

20184

30276

40368

50460

<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:

0.319

AC:

48480

AN:

152072

Hom.:

8247

Cov.:

AF XY:

0.321

AC XY:

23896

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.414

AC:

17173

AN:

41446

American (AMR)

AF:

0.374

AC:

5723

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.283

AC:

981

AN:

3472

East Asian (EAS)

AF:

0.200

AC:

1034

AN:

5158

South Asian (SAS)

AF:

0.406

AC:

1956

AN:

4816

European-Finnish (FIN)

AF:

0.267

AC:

2837

AN:

10608

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.264

AC:

17936

AN:

67962

Other (OTH)

AF:

0.297

AC:

626

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1668

3336

5004

6672

8340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<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:

0.276

Hom.:

2115

Bravo

AF:

0.329

Asia WGS

AF:

0.322

AC:

1121

AN:

3478

EpiCase

AF:

0.260

EpiControl

AF:

0.261

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

4.9

(source)

DANN

Benign

0.73

PhyloP100

-0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over