16-83994518-T-C

Position:

• chr16-83994518-T-C

Variant summary

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

The NM_019065.3(NECAB2):​c.716-91T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,593,926 control chromosomes in the GnomAD database, including 40,031 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 0.32 (14207 hom., cov: 33)
  • Exomes 𝑓: 0.16 (25824 hom.)
• Consequence: NECAB2 NM_019065.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECAB2	NM_019065.3	c.716-91T>C		intron_variant		ENST00000305202.9	NP_061938.2
NECAB2	NM_001329748.1	c.716-91T>C		intron_variant			NP_001316677.1
NECAB2	NM_001329749.2	c.467-91T>C		intron_variant			NP_001316678.1
NECAB2	XM_047434240.1	c.467-91T>C		intron_variant			XP_047290196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECAB2	ENST00000305202.9	c.716-91T>C		intron_variant		1	NM_019065.3	ENSP00000307449	P1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49130 AN: 152012 Hom.: 14150 Cov.: 33

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.290

GnomAD4 exome AF: 0.155 AC: 223728 AN: 1441794 Hom.: 25824 Cov.: 28 AF XY: 0.155 AC XY: 111536 AN XY: 718114

Gnomad4 AFR exome AF: 0.803

Gnomad4 AMR exome AF: 0.209

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.248

Gnomad4 SAS exome AF: 0.209

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.197

GnomAD4 genome AF: 0.324 AC: 49252 AN: 152132 Hom.: 14207 Cov.: 33 AF XY: 0.319 AC XY: 23708 AN XY: 74396

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.293

Alfa AF: 0.161 Hom.: 4443

Bravo AF: 0.356

Asia WGS AF: 0.301 AC: 1048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.099
DANN	Benign	0.36

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: rs2292326; hg19: chr16-84028123; COSMIC: COSV59421336; COSMIC: COSV59421336;