12-66119331-C-T

Position:

• chr12-66119331-C-T

Variant summary

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

The NM_032338.4(LLPH):​c.*4509G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 151,994 control chromosomes in the GnomAD database, including 21,474 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 (21474 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: LLPH NM_032338.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.727

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=-0.91).
• 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.*4509G>A		3_prime_UTR_variant	3/3	ENST00000266604.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LLPH	ENST00000266604.7	c.*4509G>A		3_prime_UTR_variant	3/3	1	NM_032338.4	P1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77971 AN: 151876 Hom.: 21438 Cov.: 32

Gnomad AFR AF: 0.670

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: 0.453

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.514 AC: 78057 AN: 151994 Hom.: 21474 Cov.: 32 AF XY: 0.517 AC XY: 38368 AN XY: 74272

Gnomad4 AFR AF: 0.671

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: 0.454

Alfa AF: 0.459 Hom.: 8694

Bravo AF: 0.509

Asia WGS AF: 0.666 AC: 2315 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	0.48
DANN	Benign	0.60

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

Other links and lift over

dbSNP: rs1168765; hg19: chr12-66513111;