rs2242224

Variant names:

• chr5-122425326-G-A
• rs2242224
• NM_005460.4:c.1003-26G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-122425326-G-A
• chr5-122425326-G-T

Variant summary

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

The NM_005460.4(SNCAIP):​c.1003-26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,592,538 control chromosomes in the GnomAD database, including 48,390 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 0.22 (4034 hom., cov: 33)
  • Exomes 𝑓: 0.24 (44356 hom.)
• Consequence: SNCAIP NM_005460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNCAIP	NM_005460.4	c.1003-26G>A		intron_variant	Intron 4 of 10	ENST00000261368.13	NP_005451.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNCAIP	ENST00000261368.13	c.1003-26G>A		intron_variant	Intron 4 of 10	1	NM_005460.4	ENSP00000261368.8

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32749 AN: 152030 Hom.: 4026 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.205

GnomAD3 exomes AF: 0.254 AC: 63549 AN: 250226 Hom.: 8540 AF XY: 0.257 AC XY: 34810 AN XY: 135462

Gnomad AFR exome AF: 0.0961

Gnomad AMR exome AF: 0.260

Gnomad ASJ exome AF: 0.193

Gnomad EAS exome AF: 0.267

Gnomad SAS exome AF: 0.309

Gnomad FIN exome AF: 0.327

Gnomad NFE exome AF: 0.249

Gnomad OTH exome AF: 0.254

GnomAD4 exome AF: 0.244 AC: 351070 AN: 1440390 Hom.: 44356 Cov.: 28 AF XY: 0.246 AC XY: 176916 AN XY: 717958

Gnomad4 AFR exome AF: 0.0931

Gnomad4 AMR exome AF: 0.260

Gnomad4 ASJ exome AF: 0.194

Gnomad4 EAS exome AF: 0.258

Gnomad4 SAS exome AF: 0.305

Gnomad4 FIN exome AF: 0.332

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.236

GnomAD4 genome AF: 0.215 AC: 32772 AN: 152148 Hom.: 4034 Cov.: 33 AF XY: 0.221 AC XY: 16403 AN XY: 74378

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.205

Alfa AF: 0.228 Hom.: 1319

Bravo AF: 0.200

Asia WGS AF: 0.262 AC: 909 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.42
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2242224; hg19: chr5-121761021;