dbSNP rs6944446: LRRC4:c.*1216C>T (chr7-128027463-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

7 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LRRC4	NM_022143.5 link	c.*1216C>T	3_prime_UTR_variant	Exon 2 of 2	ENST00000249363.4	NP_071426.1	Q9HBW1
SND1	NM_014390.4 link	c.1779+36407G>A	intron_variant	Intron 16 of 23	ENST00000354725.8	NP_055205.2	Q7KZF4A0A140VK49
LRRC4	XM_011516461.4 link	c.*1216C>T	3_prime_UTR_variant	Exon 3 of 3		XP_011514763.1	Q9HBW1
LRRC4	XM_047420695.1 link	c.*1216C>T	3_prime_UTR_variant	Exon 3 of 3		XP_047276651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC4	ENST00000249363.4 link	c.*1216C>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_022143.5	ENSP00000249363.3		Q9HBW1
SND1	ENST00000354725.8 link	c.1779+36407G>A		intron_variant	Intron 16 of 23	1	NM_014390.4	ENSP00000346762.3		Q7KZF4

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

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.466

AC:

194

AN:

416

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.583

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.571

AC:

86754

AN:

151838

Hom.:

25745

Cov.:

AF XY:

0.565

AC XY:

41894

AN XY:

74182

show subpopulations

African (AFR)

AF:

0.718

AC:

29714

AN:

41370

American (AMR)

AF:

0.567

AC:

8658

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.521

AC:

1807

AN:

3470

East Asian (EAS)

AF:

0.215

AC:

1107

AN:

5152

South Asian (SAS)

AF:

0.543

AC:

2613

AN:

4810

European-Finnish (FIN)

AF:

0.470

AC:

4955

AN:

10534

Middle Eastern (MID)

AF:

0.548

AC:

161

AN:

294

European-Non Finnish (NFE)

AF:

0.531

AC:

36093

AN:

67910

Other (OTH)

AF:

0.561

AC:

1182

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1821

3641

5462

7282

9103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

726

1452

2178

2904

3630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.546

Hom.:

34021

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

(source)

DANN

Benign

0.76

PhyloP100

-0.025

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over