Genetic Variant SEC14L2:n.2540T>C (chr22-30423640-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000619483.4(SEC14L2):n.2540T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,386 control chromosomes in the GnomAD database, including 7,770 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 0.32 ( 7758 hom., cov: 34)

Exomes 𝑓: 0.33 ( 12 hom. )

Consequence

SEC14L2
ENST00000619483.4 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.11

Publications

17 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:

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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=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SEC14L2	NM_012429.5 link	c.*1233T>C	3_prime_UTR_variant	Exon 12 of 12	ENST00000615189.5	NP_036561.1	O76054-1A0A024R1I5
SEC14L2	NM_001291932.2 link	c.*1233T>C	3_prime_UTR_variant	Exon 11 of 11		NP_001278861.1	B7Z3Z8
SEC14L2	NM_001204204.3 link	c.*1233T>C	3_prime_UTR_variant	Exon 10 of 10		NP_001191133.1	O76054-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC14L2	ENST00000615189.5 link	c.*1233T>C		3_prime_UTR_variant	Exon 12 of 12	1	NM_012429.5	ENSP00000478755.1		O76054-1
ENSG00000249590	ENST00000439838.5 link	c.584-3077T>C		intron_variant	Intron 6 of 8	2		ENSP00000415178.1		H7C417

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48172

AN:

152102

Hom.:

7753

Cov.:

show subpopulations

Gnomad AFR

AF:

0.328

Gnomad AMI

AF:

0.423

Gnomad AMR

AF:

0.339

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.376

Gnomad SAS

AF:

0.354

Gnomad FIN

AF:

0.343

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.297

Gnomad OTH

AF:

0.308

GnomAD4 exome

AF:

0.331

AC:

AN:

166

Hom.:

Cov.:

AF XY:

0.343

AC XY:

AN XY:

134

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.313

AC:

AN:

150

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.317

AC:

48213

AN:

152220

Hom.:

7758

Cov.:

AF XY:

0.321

AC XY:

23911

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.327

AC:

13601

AN:

41544

American (AMR)

AF:

0.338

AC:

5177

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.232

AC:

805

AN:

3470

East Asian (EAS)

AF:

0.376

AC:

1945

AN:

5172

South Asian (SAS)

AF:

0.353

AC:

1706

AN:

4832

European-Finnish (FIN)

AF:

0.343

AC:

3639

AN:

10600

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.297

AC:

20197

AN:

67980

Other (OTH)

AF:

0.315

AC:

667

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1785

3570

5356

7141

8926

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.297

Hom.:

9414

Bravo

AF:

0.313

Asia WGS

AF:

0.398

AC:

1379

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.3

(source)

DANN

Benign

0.73

PhyloP100

-1.1

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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chr22-30423640-T-C

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