rs2292326

Variant names:

• chr16-83994518-T-C
• rs2292326
• NM_019065.3:c.716-91T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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 -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 rank	MANE	Protein	UniProt
NECAB2	NM_019065.3	c.716-91T>C		intron_variant	Intron 7 of 12	ENST00000305202.9	NP_061938.2
NECAB2	NM_001329748.1	c.716-91T>C		intron_variant	Intron 7 of 11		NP_001316677.1
NECAB2	NM_001329749.2	c.467-91T>C		intron_variant	Intron 6 of 11		NP_001316678.1
NECAB2	XM_047434240.1	c.467-91T>C		intron_variant	Intron 6 of 11		XP_047290196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECAB2	ENST00000305202.9	c.716-91T>C		intron_variant	Intron 7 of 12	1	NM_019065.3	ENSP00000307449.4

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

African (AFR) AF: 0.803 AC: 26420 AN: 32916

American (AMR) AF: 0.209 AC: 9284 AN: 44330

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 4607 AN: 25962

East Asian (EAS) AF: 0.248 AC: 9811 AN: 39504

South Asian (SAS) AF: 0.209 AC: 17912 AN: 85744

European-Finnish (FIN) AF: 0.112 AC: 5944 AN: 53118

Middle Eastern (MID) AF: 0.253 AC: 1427 AN: 5646

European-Non Finnish (NFE) AF: 0.125 AC: 136563 AN: 1094882

Other (OTH) AF: 0.197 AC: 11760 AN: 59692

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

African (AFR) AF: 0.780 AC: 32344 AN: 41482

American (AMR) AF: 0.220 AC: 3371 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 613 AN: 3466

East Asian (EAS) AF: 0.260 AC: 1341 AN: 5158

South Asian (SAS) AF: 0.224 AC: 1077 AN: 4816

European-Finnish (FIN) AF: 0.111 AC: 1173 AN: 10610

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8486 AN: 67988

Other (OTH) AF: 0.293 AC: 618 AN: 2110

Alfa AF: 0.178 Hom.: 8189

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
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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