Genetic Variant SEC14L2:c.1082-896A>T (chr22-30421381-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.663

Publications

6 publications found

Variant links:

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]

SEC14L2 links:

ENSG00000249590 (HGNC:):

ENSG00000249590 links:

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]

RNF215 links:

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

RNU6-564P links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
SEC14L2	NM_012429.5 link	c.1082-896A>T	intron_variant	Intron 11 of 11	ENST00000615189.5	NP_036561.1
SEC14L2	NM_001291932.2 link	c.920-896A>T	intron_variant	Intron 10 of 10		NP_001278861.1
SEC14L2	NM_001204204.3 link	c.833-896A>T	intron_variant	Intron 9 of 9		NP_001191133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC14L2	ENST00000615189.5 link	c.1082-896A>T		intron_variant	Intron 11 of 11	1	NM_012429.5	ENSP00000478755.1
ENSG00000249590	ENST00000439838.5 link	c.583+4978A>T		intron_variant	Intron 6 of 8	2		ENSP00000415178.1

Frequencies

GnomAD3 genomes

AF:

0.540

AC:

82152

AN:

152080

Hom.:

22700

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.540

AC:

82225

AN:

152198

Hom.:

22721

Cov.:

AF XY:

0.554

AC XY:

41252

AN XY:

74406

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1951

3903

5854

7806

9757

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

724

1448

2172

2896

3620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.76

PhyloP100

-0.66

PromoterAI

0.010

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over