dbSNP rs1946649: SNCAIP:c.-46-70G>A (chr5-122391019-G-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_005460.4(SNCAIP):c.-46-70G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 795,110 control chromosomes in the GnomAD database, including 231,206 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 0.79 ( 48424 hom., cov: 32)

Exomes 𝑓: 0.75 ( 182782 hom. )

Consequence

SNCAIP
NM_005460.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.712

Publications

6 publications found

Variant links:

Genes affected

SNCAIP (HGNC:11139): (synuclein alpha interacting protein) This gene encodes a protein containing several protein-protein interaction domains, including ankyrin-like repeats, a coiled-coil domain, and an ATP/GTP-binding motif. The encoded protein interacts with alpha-synuclein in neuronal tissue and may play a role in the formation of cytoplasmic inclusions and neurodegeneration. A mutation in this gene has been associated with Parkinson's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

SNCAIP 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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005460.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SNCAIP	NM_005460.4	MANE Select	c.-46-70G>A	intron	N/A	NP_005451.2	Q9Y6H5-1
SNCAIP	NM_001308100.2		c.-46-70G>A	intron	N/A	NP_001295029.1	Q9Y6H5-3
SNCAIP	NM_001242935.3		c.-92-70G>A	intron	N/A	NP_001229864.1	Q9Y6H5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SNCAIP	ENST00000261368.13	TSL:1 MANE Select	c.-46-70G>A	intron	N/A	ENSP00000261368.8	Q9Y6H5-1
SNCAIP	ENST00000261367.11	TSL:1	c.-46-70G>A	intron	N/A	ENSP00000261367.7	Q9Y6H5-3
SNCAIP	ENST00000508017.5	TSL:1	n.-46-70G>A	intron	N/A	ENSP00000424338.1	Q6L982

Frequencies

GnomAD3 genomes

AF:

0.795

AC:

120793

AN:

152032

Hom.:

48369

Cov.:

show subpopulations

Gnomad AFR

AF:

0.892

Gnomad AMI

AF:

0.876

Gnomad AMR

AF:

0.808

Gnomad ASJ

AF:

0.688

Gnomad EAS

AF:

0.768

Gnomad SAS

AF:

0.683

Gnomad FIN

AF:

0.720

Gnomad MID

AF:

0.750

Gnomad NFE

AF:

0.758

Gnomad OTH

AF:

0.801

GnomAD4 exome

AF:

0.752

AC:

483459

AN:

642960

Hom.:

182782

AF XY:

0.747

AC XY:

260252

AN XY:

348400

show subpopulations

African (AFR)

AF:

0.893

AC:

15415

AN:

17262

American (AMR)

AF:

0.819

AC:

33889

AN:

41364

Ashkenazi Jewish (ASJ)

AF:

0.695

AC:

14436

AN:

20780

East Asian (EAS)

AF:

0.768

AC:

26787

AN:

34892

South Asian (SAS)

AF:

0.685

AC:

46723

AN:

68206

European-Finnish (FIN)

AF:

0.707

AC:

32591

AN:

46090

Middle Eastern (MID)

AF:

0.757

AC:

3106

AN:

4102

European-Non Finnish (NFE)

AF:

0.757

AC:

285279

AN:

377024

Other (OTH)

AF:

0.759

AC:

25233

AN:

33240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

6050

12101

18151

24202

30252

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2200

4400

6600

8800

11000

<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:

0.795

AC:

120908

AN:

152150

Hom.:

48424

Cov.:

AF XY:

0.790

AC XY:

58778

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.892

AC:

37064

AN:

41552

American (AMR)

AF:

0.807

AC:

12331

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.688

AC:

2386

AN:

3470

East Asian (EAS)

AF:

0.768

AC:

3971

AN:

5168

South Asian (SAS)

AF:

0.684

AC:

3288

AN:

4810

European-Finnish (FIN)

AF:

0.720

AC:

7601

AN:

10564

Middle Eastern (MID)

AF:

0.759

AC:

223

AN:

294

European-Non Finnish (NFE)

AF:

0.758

AC:

51547

AN:

67986

Other (OTH)

AF:

0.804

AC:

1698

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1243

2485

3728

4970

6213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

866

1732

2598

3464

4330

<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:

0.758

Hom.:

39106

Bravo

AF:

0.812

Asia WGS

AF:

0.754

AC:

2622

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.3

(source)

DANN

Benign

0.67

PhyloP100

-0.71

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over