NM_012429.5:c.54+111G>A

Variant names:

• chr22-30397281-G-A
• rs887098
• NM_012429.5:c.54+111G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012429.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC14L2	NM_012429.5	MANE Select	c.54+111G>A		intron	N/A	NP_036561.1
	SEC14L2	NM_033382.3		c.54+111G>A		intron	N/A	NP_203740.1
	SEC14L2	NM_001291932.2		c.-33+111G>A		intron	N/A	NP_001278861.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC14L2	ENST00000615189.5	TSL:1 MANE Select	c.54+111G>A		intron	N/A	ENSP00000478755.1
	SEC14L2	ENST00000405717.7	TSL:1	c.54+111G>A		intron	N/A	ENSP00000385186.3
	SEC14L2	ENST00000619483.4	TSL:1	n.176+111G>A		intron	N/A

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

African (AFR) AF: 0.317 AC: 5269 AN: 16620

American (AMR) AF: 0.332 AC: 5097 AN: 15366

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 3235 AN: 15354

East Asian (EAS) AF: 0.289 AC: 7932 AN: 27436

South Asian (SAS) AF: 0.314 AC: 16737 AN: 53308

European-Finnish (FIN) AF: 0.320 AC: 10956 AN: 34204

Middle Eastern (MID) AF: 0.340 AC: 949 AN: 2794

European-Non Finnish (NFE) AF: 0.265 AC: 177867 AN: 671498

Other (OTH) AF: 0.278 AC: 10946 AN: 39344

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

African (AFR) AF: 0.322 AC: 13358 AN: 41492

American (AMR) AF: 0.321 AC: 4906 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 744 AN: 3470

East Asian (EAS) AF: 0.283 AC: 1456 AN: 5138

South Asian (SAS) AF: 0.312 AC: 1507 AN: 4830

European-Finnish (FIN) AF: 0.323 AC: 3422 AN: 10582

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.279 AC: 18962 AN: 67964

Other (OTH) AF: 0.291 AC: 616 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.45
DANN	Benign	0.93
PhyloP100		-2.3
PromoterAI		-0.065	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs887098; hg19: chr22-30793270;