dbSNP rs3740569: SEC23IP:c.1102-52C>A (chr10-119908989-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_007190.4(SEC23IP):c.1102-52C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0724 in 1,195,348 control chromosomes in the GnomAD database, including 5,351 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 0.055 ( 431 hom., cov: 32)

Exomes 𝑓: 0.075 ( 4920 hom. )

Consequence

SEC23IP
NM_007190.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0470

Publications

4 publications found

Variant links:

Genes affected

SEC23IP (HGNC:17018): (SEC23 interacting protein) This gene encodes a member of the phosphatidic acid preferring-phospholipase A1 family. The encoded protein is localized to endoplasmic reticulum exit sites and plays a critical role in ER-Golgi transport as part of the multimeric coat protein II complex. An orthologous gene in frogs is required for normal neural crest cell development, suggesting that this gene may play a role in Waardenburg syndrome neural crest defects. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Feb 2011]

SEC23IP links:

Genome browser will be placed here

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=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC23IP	NM_007190.4 link	c.1102-52C>A		intron_variant	Intron 4 of 18	ENST00000369075.8	NP_009121.1	Q9Y6Y8-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SEC23IP	ENST00000369075.8 link	c.1102-52C>A	intron_variant	Intron 4 of 18	1	NM_007190.4	ENSP00000358071.3	Q9Y6Y8-1
SEC23IP	ENST00000705471.1 link	c.1102-52C>A	intron_variant	Intron 4 of 18			ENSP00000516127.1	A0A994J542
SEC23IP	ENST00000446561.1 link	c.304-3055C>A	intron_variant	Intron 2 of 4	3		ENSP00000396906.1	H7C0V8

Frequencies

GnomAD3 genomes

AF:

0.0552

AC:

8390

AN:

152044

Hom.:

431

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0121

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.0369

Gnomad ASJ

AF:

0.0378

Gnomad EAS

AF:

0.184

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.0916

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0557

Gnomad OTH

AF:

0.0441

GnomAD4 exome

AF:

0.0749

AC:

78089

AN:

1043184

Hom.:

4920

Cov.:

AF XY:

0.0812

AC XY:

43530

AN XY:

536236

show subpopulations

African (AFR)

AF:

0.0116

AC:

282

AN:

24364

American (AMR)

AF:

0.0445

AC:

1645

AN:

36946

Ashkenazi Jewish (ASJ)

AF:

0.0416

AC:

912

AN:

21908

East Asian (EAS)

AF:

0.195

AC:

7319

AN:

37556

South Asian (SAS)

AF:

0.252

AC:

18187

AN:

72254

European-Finnish (FIN)

AF:

0.0881

AC:

4620

AN:

52442

Middle Eastern (MID)

AF:

0.0701

AC:

340

AN:

4848

European-Non Finnish (NFE)

AF:

0.0554

AC:

41335

AN:

746566

Other (OTH)

AF:

0.0745

AC:

3449

AN:

46300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

3326

6652

9978

13304

16630

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1408

2816

4224

5632

7040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0552

AC:

8396

AN:

152164

Hom.:

431

Cov.:

AF XY:

0.0606

AC XY:

4504

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0121

AC:

503

AN:

41526

American (AMR)

AF:

0.0371

AC:

567

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0378

AC:

131

AN:

3470

East Asian (EAS)

AF:

0.185

AC:

957

AN:

5174

South Asian (SAS)

AF:

0.269

AC:

1296

AN:

4816

European-Finnish (FIN)

AF:

0.0916

AC:

970

AN:

10586

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0557

AC:

3788

AN:

67990

Other (OTH)

AF:

0.0455

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

377

754

1132

1509

1886

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0547

Hom.:

Bravo

AF:

0.0445

Asia WGS

AF:

0.201

AC:

699

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.63

(source)

DANN

Benign

0.55

PhyloP100

0.047

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over