Genetic Variant LLPH: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. Variant has been reported in ClinVar as (no stars).

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:

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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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032338.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LLPH	NM_032338.4	MANE Select	c.-8+30C>G		intron	N/A	NP_115714.1	Q9BRT6
	LLPH-DT	NR_125724.1		n.-76G>C		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LLPH	ENST00000266604.7	TSL:1 MANE Select	c.-8+30C>G	intron	N/A	ENSP00000266604.2	Q9BRT6
ENSG00000228144	ENST00000539652.1	TSL:2	n.*124-1562C>G	intron	N/A	ENSP00000454670.1	F6UZH7
LLPH	ENST00000446587.2	TSL:3	c.-227C>G	5_prime_UTR	Exon 1 of 3	ENSP00000437372.1	Q9BRT6

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over