22-30421381-A-T

Position:

• chr22-30421381-A-T

Variant summary

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

The NM_012429.5(SEC14L2):​c.1082-896A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 152,198 control chromosomes in the GnomAD database, including 22,721 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 0.54 (22721 hom., cov: 34)
  • Failed GnomAD Quality Control
• Consequence: SEC14L2 NM_012429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663

Genes affected

SEC14L2 (HGNC:10699): (SEC14 like lipid binding 2) This gene encodes a cytosolic protein which belongs to a family of lipid-binding proteins including Sec14p, alpha-tocopherol transfer protein, and cellular retinol-binding protein. The encoded protein stimulates squalene monooxygenase which is a downstream enzyme in the cholesterol biosynthetic pathway. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Oct 2008]

ENSG00000249590 (HGNC:):

RNF215 (HGNC:33434): (ring finger protein 215) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in Golgi to vacuole transport; protein targeting to vacuole; and ubiquitin-dependent protein catabolic process. Predicted to be integral component of membrane. Predicted to be part of Golgi transport complex. Predicted to be active in endosome; membrane; and trans-Golgi network. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC14L2	NM_012429.5	c.1082-896A>T		intron_variant		ENST00000615189.5	NP_036561.1
SEC14L2	NM_001291932.2	c.920-896A>T		intron_variant			NP_001278861.1
SEC14L2	NM_001204204.3	c.833-896A>T		intron_variant			NP_001191133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC14L2	ENST00000615189.5	c.1082-896A>T		intron_variant		1	NM_012429.5	ENSP00000478755.1
ENSG00000249590	ENST00000439838.5	c.583+4978A>T		intron_variant		2		ENSP00000415178.1

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82152 AN: 152080 Hom.: 22700 Cov.: 34

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.508

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: 0.540 AC: 82225 AN: 152198 Hom.: 22721 Cov.: 34 AF XY: 0.554 AC XY: 41252 AN XY: 74406

Gnomad4 AFR AF: 0.561

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.515

Alfa AF: 0.509 Hom.: 2463

Bravo AF: 0.531

Asia WGS AF: 0.741 AC: 2574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.76

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: rs2299829; hg19: chr22-30817370;