7-128029531-T-C

Position:

chr7-128029531-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022143.5(LRRC4):c.1110A>G(p.Ala370=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,613,924 control chromosomes in the GnomAD database, including 17,450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1555 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15895 hom. )

Consequence

LRRC4
NM_022143.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.44

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 7-128029531-T-C is Benign according to our data. Variant chr7-128029531-T-C is described in ClinVar as [Benign]. Clinvar id is 1266302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.43 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRRC4	NM_022143.5 linkuse as main transcript	c.1110A>G	p.Ala370=	synonymous_variant	2/2	ENST00000249363.4	NP_071426.1
SND1	NM_014390.4 linkuse as main transcript	c.1779+38475T>C		intron_variant		ENST00000354725.8	NP_055205.2
LRRC4	XM_011516461.4 linkuse as main transcript	c.1110A>G	p.Ala370=	synonymous_variant	3/3		XP_011514763.1
LRRC4	XM_047420695.1 linkuse as main transcript	c.1110A>G	p.Ala370=	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.1110A>G	p.Ala370=	synonymous_variant	2/2	1	NM_022143.5	ENSP00000249363	P1
SND1	ENST00000354725.8 linkuse as main transcript	c.1779+38475T>C		intron_variant		1	NM_014390.4	ENSP00000346762	P1

Frequencies

GnomAD3 genomes

AF:

0.131

AC:

19926

AN:

151990

Hom.:

1548

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0827

Gnomad AMI

AF:

0.128

Gnomad AMR

AF:

0.224

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.0864

Gnomad SAS

AF:

0.213

Gnomad FIN

AF:

0.122

Gnomad MID

AF:

0.115

Gnomad NFE

AF:

0.137

Gnomad OTH

AF:

0.129

GnomAD3 exomes

AF:

0.162

AC:

40707

AN:

251178

Hom.:

4050

AF XY:

0.159

AC XY:

21649

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.0801

Gnomad AMR exome

AF:

0.316

Gnomad ASJ exome

AF:

0.165

Gnomad EAS exome

AF:

0.0967

Gnomad SAS exome

AF:

0.200

Gnomad FIN exome

AF:

0.123

Gnomad NFE exome

AF:

0.135

Gnomad OTH exome

AF:

0.155

GnomAD4 exome

AF:

0.141

AC:

206378

AN:

1461814

Hom.:

15895

Cov.:

AF XY:

0.142

AC XY:

103426

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.0779

Gnomad4 AMR exome

AF:

0.308

Gnomad4 ASJ exome

AF:

0.168

Gnomad4 EAS exome

AF:

0.0873

Gnomad4 SAS exome

AF:

0.204

Gnomad4 FIN exome

AF:

0.120

Gnomad4 NFE exome

AF:

0.134

Gnomad4 OTH exome

AF:

0.138

GnomAD4 genome

AF:

0.131

AC:

19959

AN:

152110

Hom.:

1555

Cov.:

AF XY:

0.134

AC XY:

9968

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0828

Gnomad4 AMR

AF:

0.224

Gnomad4 ASJ

AF:

0.163

Gnomad4 EAS

AF:

0.0862

Gnomad4 SAS

AF:

0.214

Gnomad4 FIN

AF:

0.122

Gnomad4 NFE

AF:

0.137

Gnomad4 OTH

AF:

0.131

Alfa

AF:

0.119

Hom.:

658

Bravo

AF:

0.136

Asia WGS

AF:

0.177

AC:

613

AN:

3478

EpiCase

AF:

0.137

EpiControl

AF:

0.140

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

-0.84

CADD

Benign

0.58

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

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