Variant 16-84001919-AG-AGG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The ENST00000305202.9(NECAB2):c.1132+3_1132+4insG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,613,728 control chromosomes in the GnomAD database, including 19 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0056 ( 7 hom., cov: 33)

Exomes 𝑓: 0.00060 ( 12 hom. )

Consequence

NECAB2
ENST00000305202.9 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.127

Variant links:

Genes affected

NECAB2 (HGNC:23746): (N-terminal EF-hand calcium binding protein 2) The protein encoded by this gene is a neuronal calcium-binding protein that binds to and modulates the function of at least two receptors, adenosine A(2A) receptor and metabotropic glutamate receptor type 5. [provided by RefSeq, Jul 2016]

NECAB2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 16-84001919-A-AG is Benign according to our data. Variant chr16-84001919-A-AG is described in ClinVar as [Benign]. Clinvar id is 403225.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00559 (852/152290) while in subpopulation AFR AF= 0.0198 (822/41562). AF 95% confidence interval is 0.0187. There are 7 homozygotes in gnomad4. There are 392 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NECAB2	NM_019065.3 link	c.1132+8dupG	intron_variant	Intron 12 of 12	ENST00000305202.9	NP_061938.2	Q7Z6G3-1
NECAB2	NM_001329748.1 link	c.1078+8dupG	intron_variant	Intron 11 of 11		NP_001316677.1
NECAB2	NM_001329749.2 link	c.883+8dupG	intron_variant	Intron 11 of 11		NP_001316678.1	Q7Z6G3-2
NECAB2	XM_047434240.1 link	c.883+8dupG	intron_variant	Intron 11 of 11		XP_047290196.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NECAB2	ENST00000305202.9 link	c.1132+3_1132+4insG	splice_region_variant, intron_variant	Intron 12 of 12	1	NM_019065.3	ENSP00000307449.4	Q7Z6G3-1
NECAB2	ENST00000565691.5 link	c.883+3_883+4insG	splice_region_variant, intron_variant	Intron 10 of 10	1		ENSP00000457354.1	Q7Z6G3-2
NECAB2	ENST00000564166.1 link	c.157+3_157+4insG	splice_region_variant, intron_variant	Intron 2 of 2	3		ENSP00000455713.1	H3BQC7
NECAB2	ENST00000681513.1 link	n.1537+3_1537+4insG	splice_region_variant, intron_variant	Intron 12 of 12

Frequencies

GnomAD3 genomes

AF:

0.00553

AC:

842

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00150

AC:

374

AN:

250058

Hom.:

AF XY:

0.00103

AC XY:

140

AN XY:

135346

show subpopulations

Gnomad AFR exome

AF:

0.0212

Gnomad AMR exome

AF:

0.000725

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000983

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000983

GnomAD4 exome

AF:

0.000605

AC:

884

AN:

1461438

Hom.:

Cov.:

AF XY:

0.000495

AC XY:

360

AN XY:

727014

show subpopulations

Gnomad4 AFR exome

AF:

0.0217

Gnomad4 AMR exome

AF:

0.000828

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.00157

GnomAD4 genome

AF:

0.00559

AC:

852

AN:

152290

Hom.:

Cov.:

AF XY:

0.00526

AC XY:

392

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0198

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00334

Hom.:

Bravo

AF:

0.00637

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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