chr1-219173960-C-T

Variant names:

• chr1-219173960-C-T
• rs1037557668
• NM_138794.5:c.70C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001300771.2(LYPLAL1):​c.-368C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: LYPLAL1 NM_001300771.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.24
• Publications: 0 publications found

Genes affected

LYPLAL1 (HGNC:20440): (lysophospholipase like 1) Predicted to enable carboxylic ester hydrolase activity and palmitoyl-(protein) hydrolase activity. Predicted to be involved in protein depalmitoylation. Predicted to act upstream of or within negative regulation of Golgi to plasma membrane protein transport. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

LYPLAL1-DT (HGNC:50560): (LYPLAL1 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 1-219173960-C-T is Benign according to our data. Variant chr1-219173960-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 759907.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300771.2. 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
	LYPLAL1	NM_138794.5	MANE Select	c.70C>T	p.Leu24Leu	synonymous	Exon 1 of 5	NP_620149.2	Q5VWZ2-1
	LYPLAL1	NM_001300771.2		c.-368C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_001287700.1
	LYPLAL1	NM_001350628.2		c.70C>T	p.Leu24Leu	synonymous	Exon 1 of 6	NP_001337557.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYPLAL1	ENST00000366928.10	TSL:1 MANE Select	c.70C>T	p.Leu24Leu	synonymous	Exon 1 of 5	ENSP00000355895.5	Q5VWZ2-1
	LYPLAL1	ENST00000366927.3	TSL:1	c.70C>T	p.Leu24Leu	synonymous	Exon 1 of 5	ENSP00000355894.3	Q5VWZ2-2
	LYPLAL1	ENST00000474379.5	TSL:1	n.34C>T		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461738 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727194

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111950

Other (OTH) AF: 0.0000331 AC: 2 AN: 60390

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Benign	0.95
PhyloP100		1.2
PromoterAI		-0.041	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1037557668; hg19: chr1-219347302;