Variant rs6944446 details in Genebe, Genetics Data Aggregator

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

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]

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:

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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	Effect	#exon/exons	MANE
LRRC4	NM_022143.5 linkuse as main transcript	c.*1216C>T	3_prime_UTR_variant	2/2	ENST00000249363.4
SND1	NM_014390.4 linkuse as main transcript	c.1779+36407G>A	intron_variant		ENST00000354725.8
LRRC4	XM_011516461.4 linkuse as main transcript	c.*1216C>T	3_prime_UTR_variant	3/3
LRRC4	XM_047420695.1 linkuse as main transcript	c.*1216C>T	3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC4	ENST00000249363.4 linkuse as main transcript	c.*1216C>T		3_prime_UTR_variant	2/2	1	NM_022143.5	P1
SND1	ENST00000354725.8 linkuse as main transcript	c.1779+36407G>A		intron_variant		1	NM_014390.4	P1

Frequencies

GnomAD3 genomes

AF:

0.571

AC:

86673

AN:

151722

Hom.:

25721

Cov.:

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.:

Cov.:

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.:

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over