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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNCAIP	NM_005460.4 link	c.-46-70G>A		intron_variant	Intron 1 of 10	ENST00000261368.13	NP_005451.2	Q9Y6H5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNCAIP	ENST00000261368.13 link	c.-46-70G>A		intron_variant	Intron 1 of 10	1	NM_005460.4	ENSP00000261368.8		Q9Y6H5-1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over