Genetic Variant NM_053052.4:c.-45-38T>C (chr1-227747654-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_053052.4(SNAP47):c.-45-38T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 1,542,224 control chromosomes in the GnomAD database, including 281,863 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 0.68 ( 36615 hom., cov: 32)

Exomes 𝑓: 0.59 ( 245248 hom. )

Consequence

SNAP47
NM_053052.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.83

Publications

9 publications found

Variant links:

Genes affected

SNAP47 (HGNC:30669): (synaptosome associated protein 47) Predicted to enable SNAP receptor activity and syntaxin binding activity. Predicted to be involved in synaptic vesicle fusion to presynaptic active zone membrane and synaptic vesicle priming. Predicted to act upstream of or within long-term synaptic potentiation. Colocalizes with BLOC-1 complex. [provided by Alliance of Genome Resources, Apr 2022]

SNAP47 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=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP47	NM_053052.4 link	c.-45-38T>C		intron_variant	Intron 1 of 4	ENST00000617596.5	NP_444280.3	Q5SQN1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNAP47	ENST00000617596.5 link	c.-45-38T>C		intron_variant	Intron 1 of 4	1	NM_053052.4	ENSP00000483253.1		A0A087X0B7

Frequencies

GnomAD3 genomes

AF:

0.678

AC:

103076

AN:

151922

Hom.:

36548

Cov.:

show subpopulations

Gnomad AFR

AF:

0.896

Gnomad AMI

AF:

0.500

Gnomad AMR

AF:

0.679

Gnomad ASJ

AF:

0.576

Gnomad EAS

AF:

0.767

Gnomad SAS

AF:

0.631

Gnomad FIN

AF:

0.572

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.568

Gnomad OTH

AF:

0.665

GnomAD2 exomes

AF:

0.637

AC:

128178

AN:

201364

AF XY:

0.624

show subpopulations

Gnomad AFR exome

AF:

0.903

Gnomad AMR exome

AF:

0.725

Gnomad ASJ exome

AF:

0.572

Gnomad EAS exome

AF:

0.767

Gnomad FIN exome

AF:

0.570

Gnomad NFE exome

AF:

0.564

Gnomad OTH exome

AF:

0.602

GnomAD4 exome

AF:

0.590

AC:

819834

AN:

1390184

Hom.:

245248

Cov.:

AF XY:

0.589

AC XY:

401894

AN XY:

682132

show subpopulations

African (AFR)

AF:

0.909

AC:

28697

AN:

31572

American (AMR)

AF:

0.721

AC:

26813

AN:

37208

Ashkenazi Jewish (ASJ)

AF:

0.570

AC:

12364

AN:

21704

East Asian (EAS)

AF:

0.776

AC:

30224

AN:

38942

South Asian (SAS)

AF:

0.619

AC:

46153

AN:

74514

European-Finnish (FIN)

AF:

0.571

AC:

28977

AN:

50726

Middle Eastern (MID)

AF:

0.615

AC:

3337

AN:

5426

European-Non Finnish (NFE)

AF:

0.567

AC:

608224

AN:

1072868

Other (OTH)

AF:

0.612

AC:

35045

AN:

57224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

17916

35832

53747

71663

89579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17668

35336

53004

70672

88340

<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:

0.679

AC:

103200

AN:

152040

Hom.:

36615

Cov.:

AF XY:

0.678

AC XY:

50412

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.896

AC:

37185

AN:

41490

American (AMR)

AF:

0.680

AC:

10393

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.576

AC:

1998

AN:

3468

East Asian (EAS)

AF:

0.767

AC:

3949

AN:

5150

South Asian (SAS)

AF:

0.631

AC:

3035

AN:

4812

European-Finnish (FIN)

AF:

0.572

AC:

6038

AN:

10560

Middle Eastern (MID)

AF:

0.575

AC:

169

AN:

294

European-Non Finnish (NFE)

AF:

0.568

AC:

38571

AN:

67956

Other (OTH)

AF:

0.666

AC:

1406

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1567

3133

4700

6266

7833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

798

1596

2394

3192

3990

<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:

0.577

Hom.:

4832

Bravo

AF:

0.696

Asia WGS

AF:

0.684

AC:

2378

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.14

(source)

DANN

Benign

0.18

PhyloP100

-3.8

PromoterAI

0.0018

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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