rs1946649

chr5-122391019-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SNCAIP	NM_005460.4	c.-46-70G>A		intron_variant		ENST00000261368.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNCAIP	ENST00000261368.13	c.-46-70G>A		intron_variant		1	NM_005460.4	P1

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120793 AN: 152032 Hom.: 48369 Cov.: 32

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

Gnomad4 AFR exome AF: 0.893

Gnomad4 AMR exome AF: 0.819

Gnomad4 ASJ exome AF: 0.695

Gnomad4 EAS exome AF: 0.768

Gnomad4 SAS exome AF: 0.685

Gnomad4 FIN exome AF: 0.707

Gnomad4 NFE exome AF: 0.757

Gnomad4 OTH exome AF: 0.759

GnomAD4 genome AF: 0.795 AC: 120908 AN: 152150 Hom.: 48424 Cov.: 32 AF XY: 0.790 AC XY: 58778 AN XY: 74360

Gnomad4 AFR AF: 0.892

Gnomad4 AMR AF: 0.807

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.768

Gnomad4 SAS AF: 0.684

Gnomad4 FIN AF: 0.720

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.804

Alfa AF: 0.756 Hom.: 27953

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
Dann	Benign	0.67

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

LitVar

Other links and lift over

dbSNP: rs1946649; hg19: chr5-121726714; COSMIC: COSV54417465; COSMIC: COSV54417465;