Genetic Variant SYNJ2:c.1940+74C>T (chr6-158069747-C-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_003898.4(SYNJ2):c.1940+74C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,457,452 control chromosomes in the GnomAD database, including 96,091 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 0.36 ( 10313 hom., cov: 32)

Exomes 𝑓: 0.36 ( 85778 hom. )

Consequence

SYNJ2
NM_003898.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.443

Publications

10 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=-0.84).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.459 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.1940+74C>T	intron	N/A	NP_003889.1
SYNJ2	NM_001410947.1		c.1940+74C>T	intron	N/A	NP_001397876.1
SYNJ2	NM_001178088.2		c.1229+74C>T	intron	N/A	NP_001171559.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SYNJ2	ENST00000355585.9	TSL:1 MANE Select	c.1940+74C>T	intron	N/A	ENSP00000347792.4
SYNJ2	ENST00000640338.1	TSL:1	c.1940+74C>T	intron	N/A	ENSP00000492532.1
SYNJ2	ENST00000638626.1	TSL:1	c.1229+74C>T	intron	N/A	ENSP00000492369.1

Frequencies

GnomAD3 genomes

AF:

0.365

AC:

55342

AN:

151798

Hom.:

10281

Cov.:

show subpopulations

Gnomad AFR

AF:

0.327

Gnomad AMI

AF:

0.345

Gnomad AMR

AF:

0.468

Gnomad ASJ

AF:

0.430

Gnomad EAS

AF:

0.444

Gnomad SAS

AF:

0.400

Gnomad FIN

AF:

0.312

Gnomad MID

AF:

0.324

Gnomad NFE

AF:

0.360

Gnomad OTH

AF:

0.390

GnomAD4 exome

AF:

0.360

AC:

469448

AN:

1305536

Hom.:

85778

AF XY:

0.361

AC XY:

230154

AN XY:

638288

show subpopulations

African (AFR)

AF:

0.315

AC:

9394

AN:

29792

American (AMR)

AF:

0.522

AC:

17393

AN:

33324

Ashkenazi Jewish (ASJ)

AF:

0.427

AC:

8802

AN:

20604

East Asian (EAS)

AF:

0.411

AC:

14899

AN:

36272

South Asian (SAS)

AF:

0.403

AC:

23616

AN:

58618

European-Finnish (FIN)

AF:

0.302

AC:

14326

AN:

47436

Middle Eastern (MID)

AF:

0.386

AC:

1927

AN:

4996

European-Non Finnish (NFE)

AF:

0.352

AC:

359693

AN:

1021240

Other (OTH)

AF:

0.364

AC:

19398

AN:

53254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

14554

29108

43663

58217

72771

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12344

24688

37032

49376

61720

<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:

0.365

AC:

55416

AN:

151916

Hom.:

10313

Cov.:

AF XY:

0.365

AC XY:

27150

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.328

AC:

13566

AN:

41372

American (AMR)

AF:

0.468

AC:

7141

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.430

AC:

1489

AN:

3460

East Asian (EAS)

AF:

0.443

AC:

2286

AN:

5160

South Asian (SAS)

AF:

0.399

AC:

1923

AN:

4814

European-Finnish (FIN)

AF:

0.312

AC:

3298

AN:

10574

Middle Eastern (MID)

AF:

0.321

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.360

AC:

24478

AN:

67964

Other (OTH)

AF:

0.392

AC:

827

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1792

3585

5377

7170

8962

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

536

1072

1608

2144

2680

<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:

0.370

Hom.:

14936

Bravo

AF:

0.377

Asia WGS

AF:

0.422

AC:

1471

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.2

(source)

DANN

Benign

0.68

PhyloP100

-0.44

PromoterAI

0.097

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=23/77

disease causing

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over