rs887098

chr22-30397281-G-A

Variant summary

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

The NM_012429.5(SEC14L2):c.54+111G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,028,006 control chromosomes in the GnomAD database, including 39,993 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 0.30 (6923 hom., cov: 33)
  • Exomes 𝑓: 0.27 (33070 hom.)
• Consequence: SEC14L2 NM_012429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29

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]

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC14L2	NM_012429.5	c.54+111G>A		intron_variant		ENST00000615189.5
SEC14L2	NM_001204204.3	c.54+111G>A		intron_variant
SEC14L2	NM_001291932.2	c.-33+111G>A		intron_variant
SEC14L2	NM_033382.3	c.54+111G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC14L2	ENST00000615189.5	c.54+111G>A		intron_variant		1	NM_012429.5	P1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45381 AN: 151966 Hom.: 6917 Cov.: 33

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.284

GnomAD4 exome AF: 0.273 AC: 238988 AN: 875924 Hom.: 33070 AF XY: 0.275 AC XY: 119871 AN XY: 436328

Gnomad4 AFR exome AF: 0.317

Gnomad4 AMR exome AF: 0.332

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.289

Gnomad4 SAS exome AF: 0.314

Gnomad4 FIN exome AF: 0.320

Gnomad4 NFE exome AF: 0.265

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.299 AC: 45422 AN: 152082 Hom.: 6923 Cov.: 33 AF XY: 0.302 AC XY: 22466 AN XY: 74344

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.291

Alfa AF: 0.288 Hom.: 770

Bravo AF: 0.296

Asia WGS AF: 0.332 AC: 1149 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.45
Dann	Benign	0.93

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: rs887098; hg19: chr22-30793270;