chr22-30421381-A-T

Variant names:

• chr22-30421381-A-T
• rs2299829
• NM_012429.5:c.1082-896A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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]

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]

RNU6-564P (HGNC:47527): (RNA, U6 small nuclear 564, pseudogene)

ACMG classification

Our verdict: Benign. The variant received -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.

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.1082-896A>T		intron	N/A	NP_036561.1
	SEC14L2	NM_001291932.2		c.920-896A>T		intron	N/A	NP_001278861.1
	SEC14L2	NM_001204204.3		c.833-896A>T		intron	N/A	NP_001191133.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC14L2	ENST00000615189.5	TSL:1 MANE Select	c.1082-896A>T		intron	N/A	ENSP00000478755.1
	ENSG00000249590	ENST00000439838.5	TSL:2	c.583+4978A>T		intron	N/A	ENSP00000415178.1
	SEC14L2	ENST00000619483.4	TSL:1	n.1177-896A>T		intron	N/A

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

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

African (AFR) AF: 0.561 AC: 23292 AN: 41510

American (AMR) AF: 0.582 AC: 8899 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1535 AN: 3470

East Asian (EAS) AF: 0.737 AC: 3815 AN: 5176

South Asian (SAS) AF: 0.778 AC: 3754 AN: 4824

European-Finnish (FIN) AF: 0.609 AC: 6448 AN: 10592

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32755 AN: 68002

Other (OTH) AF: 0.515 AC: 1089 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.76
PhyloP100		-0.66
PromoterAI		0.010	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: rs2299829; hg19: chr22-30817370;