7-128029006-A-G

Variant summary

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

The NM_022143.5(LRRC4):ā€‹c.1635T>Cā€‹(p.Ile545=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00305 in 1,613,414 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.017 ( 80 hom., cov: 32)
Exomes š‘“: 0.0016 ( 69 hom. )

Consequence

LRRC4
NM_022143.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.64
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
Variant 7-128029006-A-G is Benign according to our data. Variant chr7-128029006-A-G is described in ClinVar as [Benign]. Clinvar id is 776259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.64 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0555 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LRRC4NM_022143.5 linkuse as main transcriptc.1635T>C p.Ile545= synonymous_variant 2/2 ENST00000249363.4 NP_071426.1
SND1NM_014390.4 linkuse as main transcriptc.1779+37950A>G intron_variant ENST00000354725.8 NP_055205.2
LRRC4XM_011516461.4 linkuse as main transcriptc.1635T>C p.Ile545= synonymous_variant 3/3 XP_011514763.1
LRRC4XM_047420695.1 linkuse as main transcriptc.1635T>C p.Ile545= synonymous_variant 3/3 XP_047276651.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LRRC4ENST00000249363.4 linkuse as main transcriptc.1635T>C p.Ile545= synonymous_variant 2/21 NM_022143.5 ENSP00000249363 P1
SND1ENST00000354725.8 linkuse as main transcriptc.1779+37950A>G intron_variant 1 NM_014390.4 ENSP00000346762 P1

Frequencies

GnomAD3 genomes
AF:
0.0166
AC:
2527
AN:
151998
Hom.:
79
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0574
Gnomad AMI
AF:
0.0252
Gnomad AMR
AF:
0.00675
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00862
GnomAD3 exomes
AF:
0.00447
AC:
1117
AN:
250068
Hom.:
31
AF XY:
0.00321
AC XY:
434
AN XY:
135236
show subpopulations
Gnomad AFR exome
AF:
0.0617
Gnomad AMR exome
AF:
0.00288
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000164
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000115
Gnomad OTH exome
AF:
0.00131
GnomAD4 exome
AF:
0.00164
AC:
2390
AN:
1461298
Hom.:
69
Cov.:
31
AF XY:
0.00136
AC XY:
987
AN XY:
726888
show subpopulations
Gnomad4 AFR exome
AF:
0.0578
Gnomad4 AMR exome
AF:
0.00336
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000105
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000477
Gnomad4 OTH exome
AF:
0.00384
GnomAD4 genome
AF:
0.0166
AC:
2532
AN:
152116
Hom.:
80
Cov.:
32
AF XY:
0.0158
AC XY:
1178
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.0574
Gnomad4 AMR
AF:
0.00674
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00853
Alfa
AF:
0.00604
Hom.:
4
Bravo
AF:
0.0183
Asia WGS
AF:
0.00520
AC:
19
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxNov 12, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
CADD
Benign
4.8
DANN
Benign
0.67

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.

Other links and lift over

dbSNP: rs73721283; hg19: chr7-127669059; API