Variant 6-33419822-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The XM_047419455.1(SYNGAP1):c.-18+1440G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 153,928 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.012 ( 21 hom., cov: 30)

Exomes 𝑓: 0.0054 ( 0 hom. )

Consequence

SYNGAP1
XM_047419455.1 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.54

Variant links:

Genes affected

SYNGAP1 (HGNC:11497): (synaptic Ras GTPase activating protein 1) This gene encodes a Ras GTPase activating protein that is a member of the N-methyl-D-aspartate receptor complex. The N-terminal domain of the protein contains a Ras-GAP domain, a pleckstrin homology domain, and a C2 domain that may be involved in binding of calcium and phospholipids. The C-terminal domain consists of a ten histidine repeat region, serine and tyrosine phosphorylation sites, and a T/SXV motif required for postsynaptic scaffold protein interaction. The encoded protein negatively regulates Ras, Rap and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor trafficking to the postsynaptic membrane to regulate synaptic plasticity and neuronal homeostasis. Allelic variants of this gene are associated with intellectual disability and autism spectrum disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

SYNGAP1 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=-0.48).

BP6

Variant 6-33419822-G-C is Benign according to our data. Variant chr6-33419822-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1204001.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0119 (1802/151894) while in subpopulation AFR AF= 0.0212 (877/41404). AF 95% confidence interval is 0.02. There are 21 homozygotes in gnomad4. There are 919 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1802 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNGAP1	XM_047419455.1 linkuse as main transcript	c.-18+1440G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNGAP1	ENST00000637194.1 linkuse as main transcript	n.39+123G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0119

AC:

1803

AN:

151776

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0212

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.00735

Gnomad SAS

AF:

0.0125

Gnomad FIN

AF:

0.00199

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00802

Gnomad OTH

AF:

0.00960

GnomAD4 exome

AF:

0.00541

AC:

AN:

2034

Hom.:

Cov.:

AF XY:

0.00618

AC XY:

AN XY:

1294

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0135

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0152

Gnomad4 SAS exome

AF:

0.00836

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00356

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0119

AC:

1802

AN:

151894

Hom.:

Cov.:

AF XY:

0.0124

AC XY:

919

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.0212

Gnomad4 AMR

AF:

0.0107

Gnomad4 ASJ

AF:

0.0173

Gnomad4 EAS

AF:

0.00736

Gnomad4 SAS

AF:

0.0125

Gnomad4 FIN

AF:

0.00199

Gnomad4 NFE

AF:

0.00803

Gnomad4 OTH

AF:

0.00950

Alfa

AF:

0.00963

Hom.:

Bravo

AF:

0.0134

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.84

Splicing

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