chr12-66119331-C-T

Variant names:

• chr12-66119331-C-T
• rs1168765
• NM_032338.4:c.*4509G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LLPH	NM_032338.4	c.*4509G>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000266604.7	NP_115714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LLPH	ENST00000266604.7	c.*4509G>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_032338.4	ENSP00000266604.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.671 AC: 27806 AN: 41448

American (AMR) AF: 0.355 AC: 5427 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1794 AN: 3470

East Asian (EAS) AF: 0.850 AC: 4391 AN: 5164

South Asian (SAS) AF: 0.552 AC: 2658 AN: 4818

European-Finnish (FIN) AF: 0.486 AC: 5111 AN: 10526

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29435 AN: 67962

Other (OTH) AF: 0.454 AC: 957 AN: 2108

Alfa AF: 0.460 Hom.: 9644

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
PhyloP100		-0.73

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

Other links and lift over

dbSNP: rs1168765; hg19: chr12-66513111;