rs1177578

chr12-66130675-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
LLPH	NM_032338.4	c.-8+30C>G		intron_variant		ENST00000266604.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LLPH	ENST00000266604.7	c.-8+30C>G		intron_variant		1	NM_032338.4	P1
LLPH	ENST00000446587.2	c.-227C>G		5_prime_UTR_variant	1/3	3		P1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78189 AN: 151992 Hom.: 21573 Cov.: 33

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: 47 AN: 98 Hom.: 14 Cov.: 0 AF XY: 0.500 AC XY: 35 AN XY: 70

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.550

Gnomad4 NFE exome AF: 0.453

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.515 AC: 78275 AN: 152108 Hom.: 21609 Cov.: 33 AF XY: 0.518 AC XY: 38484 AN XY: 74344

Gnomad4 AFR AF: 0.675

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.850

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.455

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
Dann	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

LitVar

Other links and lift over

dbSNP: rs1177578; hg19: chr12-66524455;