chr16-84001919-A-AG

Variant names:

• chr16-84001919-A-AG
• rs113413576
• NM_019065.3:c.1132+8dupG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.127
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000305202.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECAB2	NM_019065.3	MANE Select	c.1132+8dupG		intron	N/A	NP_061938.2
	NECAB2	NM_001329748.1		c.1078+8dupG		intron	N/A	NP_001316677.1
	NECAB2	NM_001329749.2		c.883+8dupG		intron	N/A	NP_001316678.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECAB2	ENST00000305202.9	TSL:1 MANE Select	c.1132+3_1132+4insG		splice_region intron	N/A	ENSP00000307449.4
	NECAB2	ENST00000565691.5	TSL:1	c.883+3_883+4insG		splice_region intron	N/A	ENSP00000457354.1
	NECAB2	ENST00000564166.1	TSL:3	c.157+3_157+4insG		splice_region intron	N/A	ENSP00000455713.1

Frequencies

GnomAD3 genomes AF: 0.00553 AC: 842 AN: 152172 Hom.: 5 Cov.: 33

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

GnomAD2 exomes AF: 0.00150 AC: 374 AN: 250058 AF XY: 0.00103

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 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.: 12 Cov.: 32 AF XY: 0.000495 AC XY: 360 AN XY: 727014

African (AFR) AF: 0.0217 AC: 727 AN: 33460

American (AMR) AF: 0.000828 AC: 37 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5756

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111734

Other (OTH) AF: 0.00157 AC: 95 AN: 60384

GnomAD4 genome AF: 0.00559 AC: 852 AN: 152290 Hom.: 7 Cov.: 33 AF XY: 0.00526 AC XY: 392 AN XY: 74462

African (AFR) AF: 0.0198 AC: 822 AN: 41562

American (AMR) AF: 0.00131 AC: 20 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68002

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00334 Hom.: 0

Bravo AF: 0.00637

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs113413576; hg19: chr16-84035524;