rs7587426

chr2-162353833-C-T

Variant summary

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

The NM_012198.5(GCA):c.262+1426C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,978 control chromosomes in the GnomAD database, including 13,328 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 0.39 (13328 hom., cov: 32)
• Consequence: GCA NM_012198.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530

Genes affected

GCA (HGNC:15990): (grancalcin) This gene encodes a calcium-binding protein that is abundant in neutrophils and macrophages. In the absence of divalent cation, this protein localizes to the cytosolic fraction; with magnesium alone, it partitions with the granule fraction; and in the presence of magnesium and calcium, it associates with both the granule and membrane fractions. Alternative splicing and use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCA	NM_012198.5	c.262+1426C>T		intron_variant		ENST00000437150.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCA	ENST00000437150.7	c.262+1426C>T		intron_variant		1	NM_012198.5	P1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58634 AN: 151860 Hom.: 13329 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.0153

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.386 AC: 58626 AN: 151978 Hom.: 13328 Cov.: 32 AF XY: 0.379 AC XY: 28149 AN XY: 74282

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.0153

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.414

Alfa AF: 0.499 Hom.: 16434

Bravo AF: 0.369

Asia WGS AF: 0.189 AC: 658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.2
Dann	Benign	0.65

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: rs7587426; hg19: chr2-163210343;