Variant chr16-9755072-A-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 NM_001134407.3(GRIN2A):c.*8077T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 199,214 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 27 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 1 hom. )

Consequence

GRIN2A
NM_001134407.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.412

Variant links:

Genes affected

GRIN2A (HGNC:4585): (glutamate ionotropic receptor NMDA type subunit 2A) This gene encodes a member of the glutamate-gated ion channel protein family. The encoded protein is an N-methyl-D-aspartate (NMDA) receptor subunit. NMDA receptors are both ligand-gated and voltage-dependent, and are involved in long-term potentiation, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certain kinds of memory and learning. These receptors are permeable to calcium ions, and activation results in a calcium influx into post-synaptic cells, which results in the activation of several signaling cascades. Disruption of this gene is associated with focal epilepsy and speech disorder with or without cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

GRIN2A 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=-0.8).

BP6

Variant 16-9755072-A-C is Benign according to our data. Variant chr16-9755072-A-C is described in ClinVar as [Benign]. Clinvar id is 321476.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1885/152304) while in subpopulation AFR AF= 0.0425 (1766/41562). AF 95% confidence interval is 0.0408. There are 27 homozygotes in gnomad4. There are 915 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1885 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN2A	NM_001134407.3 linkuse as main transcript	c.*8077T>G		3_prime_UTR_variant	13/13	ENST00000330684.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN2A	ENST00000330684.4 linkuse as main transcript	c.*8077T>G		3_prime_UTR_variant	13/13	1	NM_001134407.3	P1	Q12879-1
GRIN2A	ENST00000396573.6 linkuse as main transcript	c.*8077T>G		3_prime_UTR_variant	14/14	1		P1	Q12879-1

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1877

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0424

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00577

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00812

GnomAD4 exome

AF:

0.00243

AC:

114

AN:

46910

Hom.:

Cov.:

AF XY:

0.00202

AC XY:

AN XY:

21732

show subpopulations

Gnomad4 AFR exome

AF:

0.0460

Gnomad4 AMR exome

AF:

0.00679

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000703

Gnomad4 OTH exome

AF:

0.00356

GnomAD4 genome

AF:

0.0124

AC:

1885

AN:

152304

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

915

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0425

Gnomad4 AMR

AF:

0.00569

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00803

Alfa

AF:

0.0106

Hom.:

Bravo

AF:

0.0144

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Landau-Kleffner syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.7

DANN

Benign

0.82

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

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