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

new If you want to explore the variant's impact on the transcript NM_007190.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007190.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SEC23IP	NM_007190.4	MANE Select	c.1102-52C>A	intron	N/A	NP_009121.1	Q9Y6Y8-1
SEC23IP	NM_001411070.1		c.1102-52C>A	intron	N/A	NP_001397999.1	A0A994J542
SEC23IP	NR_037771.2		n.622-52C>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SEC23IP	ENST00000369075.8	TSL:1 MANE Select	c.1102-52C>A	intron	N/A	ENSP00000358071.3	Q9Y6Y8-1
SEC23IP	ENST00000875162.1		c.1102-52C>A	intron	N/A	ENSP00000545221.1
SEC23IP	ENST00000970232.1		c.1102-52C>A	intron	N/A	ENSP00000640291.1

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over