7-128029804-A-T

Position:

chr7-128029804-A-T

Variant summary

Our verdict is Benign. Variant got -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

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:

SND1 (HGNC:):

SND1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC4	NM_022143.5 linkuse as main transcript	c.837T>A	p.Ser279Ser	synonymous_variant	2/2	ENST00000249363.4	NP_071426.1	Q9HBW1
SND1	NM_014390.4 linkuse as main transcript	c.1779+38748A>T		intron_variant		ENST00000354725.8	NP_055205.2	Q7KZF4A0A140VK49
LRRC4	XM_011516461.4 linkuse as main transcript	c.837T>A	p.Ser279Ser	synonymous_variant	3/3		XP_011514763.1	Q9HBW1
LRRC4	XM_047420695.1 linkuse as main transcript	c.837T>A	p.Ser279Ser	synonymous_variant	3/3		XP_047276651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC4	ENST00000249363.4 linkuse as main transcript	c.837T>A	p.Ser279Ser	synonymous_variant	2/2	1	NM_022143.5	ENSP00000249363.3		Q9HBW1
SND1	ENST00000354725.8 linkuse as main transcript	c.1779+38748A>T		intron_variant		1	NM_014390.4	ENSP00000346762.3		Q7KZF4

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

GnomAD3 exomes

AF:

0.309

AC:

77595

AN:

250930

Hom.:

12762

AF XY:

0.304

AC XY:

41336

AN XY:

135780

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 SAS exome

AF:

0.381

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

Gnomad4 AFR exome

AF:

0.423

Gnomad4 AMR exome

AF:

0.426

Gnomad4 ASJ exome

AF:

0.279

Gnomad4 EAS exome

AF:

0.190

Gnomad4 SAS exome

AF:

0.380

Gnomad4 FIN exome

AF:

0.268

Gnomad4 NFE exome

AF:

0.263

Gnomad4 OTH exome

AF:

0.278

GnomAD4 genome

AF:

0.319

AC:

48480

AN:

152072

Hom.:

8247

Cov.:

AF XY:

0.321

AC XY:

23896

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.414

Gnomad4 AMR

AF:

0.374

Gnomad4 ASJ

AF:

0.283

Gnomad4 EAS

AF:

0.200

Gnomad4 SAS

AF:

0.406

Gnomad4 FIN

AF:

0.267

Gnomad4 NFE

AF:

0.264

Gnomad4 OTH

AF:

0.297

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

4.9

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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