16-83981077-C-T

Variant names:

• chr16-83981077-C-T
• rs150547119
• NM_019065.3:c.409C>T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_019065.3(NECAB2):​c.409C>T​(p.Leu137Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,128 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 32)
• Consequence: NECAB2 NM_019065.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.219

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP7: Synonymous conserved (PhyloP=0.219 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECAB2	NM_019065.3	c.409C>T	p.Leu137Leu	synonymous_variant	Exon 5 of 13	ENST00000305202.9	NP_061938.2
NECAB2	NM_001329748.1	c.409C>T	p.Leu137Leu	synonymous_variant	Exon 5 of 12		NP_001316677.1
NECAB2	NM_001329749.2	c.160C>T	p.Leu54Leu	synonymous_variant	Exon 4 of 12		NP_001316678.1
NECAB2	XM_047434240.1	c.160C>T	p.Leu54Leu	synonymous_variant	Exon 4 of 12		XP_047290196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECAB2	ENST00000305202.9	c.409C>T	p.Leu137Leu	synonymous_variant	Exon 5 of 13	1	NM_019065.3	ENSP00000307449.4
NECAB2	ENST00000565691.5	c.160C>T	p.Leu54Leu	synonymous_variant	Exon 3 of 11	1		ENSP00000457354.1
NECAB2	ENST00000566836.1	c.82C>T	p.Leu28Leu	synonymous_variant	Exon 3 of 7	5		ENSP00000455322.1
NECAB2	ENST00000681513.1	n.814C>T		non_coding_transcript_exon_variant	Exon 5 of 13

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152128 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152128 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74310

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

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: 0.00

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	5.8
DANN	Benign	0.80

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: rs150547119; hg19: chr16-84014682;