Variant chr5-176629805-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000310112.7(SNCB):c.-10+4G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.985 in 1,160,720 control chromosomes in the GnomAD database, including 564,749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.93 ( 66806 hom., cov: 29)

Exomes 𝑓: 0.99 ( 497943 hom. )

Consequence

SNCB
ENST00000310112.7 splice_donor_region, intron

Scores

Splicing: ADA: 0.00001992

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: 0.233

Variant links:

Genes affected

SNCB (HGNC:11140): (synuclein beta) This gene encodes a member of a small family of proteins that inhibit phospholipase D2 and may function in neuronal plasticity. The encoded protein is abundant in lesions of patients with Alzheimer disease. A mutation in this gene was found in individuals with dementia with Lewy bodies. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

SNCB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 5-176629805-C-T is Benign according to our data. Variant chr5-176629805-C-T is described in ClinVar as [Benign]. Clinvar id is 1181147.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-176629805-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNCB	NM_003085.5 linkuse as main transcript	c.-9-142G>A		intron_variant		ENST00000393693.7	NP_003076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNCB	ENST00000393693.7 linkuse as main transcript	c.-9-142G>A		intron_variant		1	NM_003085.5	ENSP00000377296	P1

Frequencies

GnomAD3 genomes

AF:

0.932

AC:

141476

AN:

151796

Hom.:

66771

Cov.:

show subpopulations

Gnomad AFR

AF:

0.765

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.972

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.991

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.943

GnomAD4 exome

AF:

0.993

AC:

1001631

AN:

1008806

Hom.:

497943

Cov.:

AF XY:

0.994

AC XY:

494020

AN XY:

497184

show subpopulations

Gnomad4 AFR exome

AF:

0.758

Gnomad4 AMR exome

AF:

0.984

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.999

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.999

Gnomad4 OTH exome

AF:

0.983

GnomAD4 genome

AF:

0.932

AC:

141570

AN:

151914

Hom.:

66806

Cov.:

AF XY:

0.933

AC XY:

69273

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.765

Gnomad4 AMR

AF:

0.972

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.944

Alfa

AF:

0.967

Hom.:

10993

Bravo

AF:

0.921

Asia WGS

AF:

0.988

AC:

3436

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

9.7

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000020

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over