Genetic Variant NM_032338.4:c.-8+30C>G (chr12-66130675-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032338.4(LLPH):c.-8+30C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 152,206 control chromosomes in the GnomAD database, including 21,623 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 0.51 ( 21609 hom., cov: 33)

Exomes 𝑓: 0.48 ( 14 hom. )

Consequence

LLPH
NM_032338.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.15

Publications

13 publications found

Variant links:

Genes affected

LLPH (HGNC:28229): (LLP homolog, long-term synaptic facilitation factor) Enables RNA binding activity. Predicted to be involved in dendrite extension and positive regulation of dendritic spine development. Located in chromosome and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

LLPH links:

ENSG00000228144 (HGNC:):

ENSG00000228144 links:

LLPH-DT (HGNC:50493): (LLPH divergent transcript)

LLPH-DT 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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LLPH	NM_032338.4 link	c.-8+30C>G		intron_variant	Intron 1 of 2	ENST00000266604.7	NP_115714.1	Q9BRT6A0A024RB76
LLPH-DT	NR_125724.1 link	n.-76G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LLPH	ENST00000266604.7 link	c.-8+30C>G	intron_variant	Intron 1 of 2	1	NM_032338.4	ENSP00000266604.2	Q9BRT6
ENSG00000228144	ENST00000539652.1 link	n.*124-1562C>G	intron_variant	Intron 6 of 7	2		ENSP00000454670.1	F6UZH7
LLPH	ENST00000446587.2 link	c.-227C>G	5_prime_UTR_variant	Exon 1 of 3	3		ENSP00000437372.1	Q9BRT6
LLPH-DT	ENST00000510317.2 link	n.-76G>C	upstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.514

AC:

78189

AN:

151992

Hom.:

21573

Cov.:

show subpopulations

Gnomad AFR

AF:

0.674

Gnomad AMI

AF:

0.377

Gnomad AMR

AF:

0.355

Gnomad ASJ

AF:

0.517

Gnomad EAS

AF:

0.850

Gnomad SAS

AF:

0.552

Gnomad FIN

AF:

0.486

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.433

Gnomad OTH

AF:

0.454

GnomAD4 exome

AF:

0.480

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.550

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.453

AC:

AN:

Other (OTH)

AF:

0.375

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.515

AC:

78275

AN:

152108

Hom.:

21609

Cov.:

AF XY:

0.518

AC XY:

38484

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.675

AC:

28017

AN:

41522

American (AMR)

AF:

0.355

AC:

5424

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.517

AC:

1794

AN:

3468

East Asian (EAS)

AF:

0.850

AC:

4391

AN:

5164

South Asian (SAS)

AF:

0.552

AC:

2664

AN:

4828

European-Finnish (FIN)

AF:

0.486

AC:

5126

AN:

10556

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.433

AC:

29424

AN:

67974

Other (OTH)

AF:

0.455

AC:

958

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1799

3598

5396

7195

8994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

682

1364

2046

2728

3410

<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:

0.467

Hom.:

2167

Bravo

AF:

0.510

Asia WGS

AF:

0.665

AC:

2313

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.4

(source)

DANN

Benign

0.51

PhyloP100

-1.1

PromoterAI

0.13

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=299/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over