8-90804417-A-G

Variant names:

• chr8-90804417-A-G
• rs7825213
• NM_022351.5:c.124+2702A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022351.5(NECAB1):​c.124+2702A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,640 control chromosomes in the GnomAD database, including 19,635 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 0.48 (19635 hom., cov: 30)
• Consequence: NECAB1 NM_022351.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 0 publications found

Genes affected

NECAB1 (HGNC:20983): (N-terminal EF-hand calcium binding protein 1) Enables identical protein binding activity. Predicted to be involved in regulation of amyloid precursor protein biosynthetic process. Predicted to act upstream of or within blastocyst hatching. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECAB1	NM_022351.5	c.124+2702A>G		intron_variant	Intron 2 of 12	ENST00000417640.7	NP_071746.1
NECAB1	XM_011517213.3	c.124+2702A>G		intron_variant	Intron 2 of 11		XP_011515515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECAB1	ENST00000417640.7	c.124+2702A>G		intron_variant	Intron 2 of 12	1	NM_022351.5	ENSP00000387380.2
NECAB1	ENST00000521954.1	n.201+2702A>G		intron_variant	Intron 2 of 5	2
NECAB1	ENST00000522729.5	n.270+2702A>G		intron_variant	Intron 2 of 2	2
NECAB1	ENST00000523962.5	n.201+2702A>G		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72715 AN: 151522 Hom.: 19607 Cov.: 30

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.480 AC: 72802 AN: 151640 Hom.: 19635 Cov.: 30 AF XY: 0.484 AC XY: 35854 AN XY: 74102

African (AFR) AF: 0.682 AC: 28151 AN: 41284

American (AMR) AF: 0.550 AC: 8395 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1018 AN: 3462

East Asian (EAS) AF: 0.857 AC: 4392 AN: 5122

South Asian (SAS) AF: 0.424 AC: 2030 AN: 4792

European-Finnish (FIN) AF: 0.407 AC: 4290 AN: 10540

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.343 AC: 23252 AN: 67878

Other (OTH) AF: 0.462 AC: 973 AN: 2106

Alfa AF: 0.412 Hom.: 1782

Bravo AF: 0.506

Asia WGS AF: 0.660 AC: 2294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.89
PhyloP100		0.35
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: rs7825213; hg19: chr8-91816645;