rs9937660

Positions:

• chr16-83994926-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019065.3(NECAB2):​c.795+238A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,152 control chromosomes in the GnomAD database, including 4,412 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (4412 hom., cov: 33)
• Consequence: NECAB2 NM_019065.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECAB2	NM_019065.3	c.795+238A>G		intron_variant		ENST00000305202.9	NP_061938.2
NECAB2	NM_001329748.1	c.795+238A>G		intron_variant			NP_001316677.1
NECAB2	NM_001329749.2	c.546+238A>G		intron_variant			NP_001316678.1
NECAB2	XM_047434240.1	c.546+238A>G		intron_variant			XP_047290196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECAB2	ENST00000305202.9	c.795+238A>G		intron_variant		1	NM_019065.3	ENSP00000307449	P1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27894 AN: 152034 Hom.: 4377 Cov.: 33

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0718

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0723

Gnomad OTH AF: 0.175

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.184 AC: 27985 AN: 152152 Hom.: 4412 Cov.: 33 AF XY: 0.181 AC XY: 13484 AN XY: 74390

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0718

Gnomad4 NFE AF: 0.0723

Gnomad4 OTH AF: 0.180

Alfa AF: 0.106 Hom.: 1129

Bravo AF: 0.204

Asia WGS AF: 0.165 AC: 575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.59
DANN	Benign	0.29

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

Other links and lift over

dbSNP: rs9937660; hg19: chr16-84028531;