rs6944446

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022143.5(LRRC4):​c.*1216C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,274 control chromosomes in the GnomAD database, including 25,799 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 25745 hom., cov: 31)
Exomes 𝑓: 0.47 ( 54 hom. )

Consequence

LRRC4
NM_022143.5 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0250
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LRRC4NM_022143.5 linkuse as main transcriptc.*1216C>T 3_prime_UTR_variant 2/2 ENST00000249363.4
SND1NM_014390.4 linkuse as main transcriptc.1779+36407G>A intron_variant ENST00000354725.8
LRRC4XM_011516461.4 linkuse as main transcriptc.*1216C>T 3_prime_UTR_variant 3/3
LRRC4XM_047420695.1 linkuse as main transcriptc.*1216C>T 3_prime_UTR_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LRRC4ENST00000249363.4 linkuse as main transcriptc.*1216C>T 3_prime_UTR_variant 2/21 NM_022143.5 P1
SND1ENST00000354725.8 linkuse as main transcriptc.1779+36407G>A intron_variant 1 NM_014390.4 P1

Frequencies

GnomAD3 genomes
AF:
0.571
AC:
86673
AN:
151722
Hom.:
25721
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.718
Gnomad AMI
AF:
0.510
Gnomad AMR
AF:
0.566
Gnomad ASJ
AF:
0.521
Gnomad EAS
AF:
0.216
Gnomad SAS
AF:
0.544
Gnomad FIN
AF:
0.470
Gnomad MID
AF:
0.535
Gnomad NFE
AF:
0.532
Gnomad OTH
AF:
0.561
GnomAD4 exome
AF:
0.472
AC:
206
AN:
436
Hom.:
54
Cov.:
0
AF XY:
0.485
AC XY:
129
AN XY:
266
show subpopulations
Gnomad4 AFR exome
AF:
1.00
Gnomad4 FIN exome
AF:
0.466
Gnomad4 NFE exome
AF:
0.583
Gnomad4 OTH exome
AF:
0.500
GnomAD4 genome
AF:
0.571
AC:
86754
AN:
151838
Hom.:
25745
Cov.:
31
AF XY:
0.565
AC XY:
41894
AN XY:
74182
show subpopulations
Gnomad4 AFR
AF:
0.718
Gnomad4 AMR
AF:
0.567
Gnomad4 ASJ
AF:
0.521
Gnomad4 EAS
AF:
0.215
Gnomad4 SAS
AF:
0.543
Gnomad4 FIN
AF:
0.470
Gnomad4 NFE
AF:
0.531
Gnomad4 OTH
AF:
0.561
Alfa
AF:
0.540
Hom.:
22494
Bravo
AF:
0.581
Asia WGS
AF:
0.413
AC:
1438
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
5.9
DANN
Benign
0.76

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: rs6944446; hg19: chr7-127667516; COSMIC: COSV50815731; COSMIC: COSV50815731; API