Genetic Variant NM_003898.4:c.2450-193T>C (chr6-158077971-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 NM_003898.4(SYNJ2):c.2450-193T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 501,368 control chromosomes in the GnomAD database, including 68,695 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 0.55 ( 23793 hom., cov: 32)

Exomes 𝑓: 0.50 ( 44902 hom. )

Consequence

SYNJ2
NM_003898.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.11

Publications

4 publications found

Variant links:

Genes affected

SYNJ2 (HGNC:11504): (synaptojanin 2) The gene is a member of the inositol-polyphosphate 5-phosphatase family. The encoded protein interacts with the ras-related C3 botulinum toxin substrate 1, which causes translocation of the encoded protein to the plasma membrane where it inhibits clathrin-mediated endocytosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

SYNJ2 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=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003898.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SYNJ2	NM_003898.4	MANE Select	c.2450-193T>C	intron	N/A	NP_003889.1
SYNJ2	NM_001410947.1		c.2450-193T>C	intron	N/A	NP_001397876.1
SYNJ2	NM_001178088.2		c.1739-193T>C	intron	N/A	NP_001171559.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SYNJ2	ENST00000355585.9	TSL:1 MANE Select	c.2450-193T>C	intron	N/A	ENSP00000347792.4
SYNJ2	ENST00000640338.1	TSL:1	c.2450-193T>C	intron	N/A	ENSP00000492532.1
SYNJ2	ENST00000638626.1	TSL:1	c.1739-193T>C	intron	N/A	ENSP00000492369.1

Frequencies

GnomAD3 genomes

AF:

0.552

AC:

83847

AN:

151910

Hom.:

23766

Cov.:

show subpopulations

Gnomad AFR

AF:

0.687

Gnomad AMI

AF:

0.699

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.465

Gnomad EAS

AF:

0.573

Gnomad SAS

AF:

0.507

Gnomad FIN

AF:

0.552

Gnomad MID

AF:

0.420

Gnomad NFE

AF:

0.511

Gnomad OTH

AF:

0.536

GnomAD4 exome

AF:

0.501

AC:

175043

AN:

349340

Hom.:

44902

Cov.:

AF XY:

0.498

AC XY:

93051

AN XY:

186968

show subpopulations

African (AFR)

AF:

0.689

AC:

7290

AN:

10582

American (AMR)

AF:

0.344

AC:

4785

AN:

13920

Ashkenazi Jewish (ASJ)

AF:

0.468

AC:

4772

AN:

10198

East Asian (EAS)

AF:

0.510

AC:

12225

AN:

23966

South Asian (SAS)

AF:

0.482

AC:

18786

AN:

38950

European-Finnish (FIN)

AF:

0.533

AC:

12133

AN:

22754

Middle Eastern (MID)

AF:

0.422

AC:

604

AN:

1432

European-Non Finnish (NFE)

AF:

0.502

AC:

104333

AN:

207976

Other (OTH)

AF:

0.517

AC:

10115

AN:

19562

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

4022

8044

12067

16089

20111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

636

1272

1908

2544

3180

<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:

0.552

AC:

83907

AN:

152028

Hom.:

23793

Cov.:

AF XY:

0.550

AC XY:

40875

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.686

AC:

28457

AN:

41456

American (AMR)

AF:

0.391

AC:

5975

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.465

AC:

1611

AN:

3468

East Asian (EAS)

AF:

0.573

AC:

2965

AN:

5172

South Asian (SAS)

AF:

0.506

AC:

2440

AN:

4824

European-Finnish (FIN)

AF:

0.552

AC:

5820

AN:

10538

Middle Eastern (MID)

AF:

0.432

AC:

126

AN:

292

European-Non Finnish (NFE)

AF:

0.511

AC:

34749

AN:

67970

Other (OTH)

AF:

0.535

AC:

1128

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1905

3810

5715

7620

9525

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

726

1452

2178

2904

3630

<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:

0.517

Hom.:

10552

Bravo

AF:

0.547

Asia WGS

AF:

0.555

AC:

1931

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.20

(source)

DANN

Benign

0.37

PhyloP100

-2.1

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over