rs3788964

chr2-162350970-T-C

Variant summary

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

The NM_012198.5(GCA):c.193-1368T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,172 control chromosomes in the GnomAD database, including 1,758 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 0.13 (1758 hom., cov: 32)
• Consequence: GCA NM_012198.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCA	NM_012198.5	c.193-1368T>C		intron_variant		ENST00000437150.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCA	ENST00000437150.7	c.193-1368T>C		intron_variant		1	NM_012198.5	P1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19572 AN: 152054 Hom.: 1761 Cov.: 32

Gnomad AFR AF: 0.0303

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.0945

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.128 AC: 19551 AN: 152172 Hom.: 1758 Cov.: 32 AF XY: 0.132 AC XY: 9816 AN XY: 74394

Gnomad4 AFR AF: 0.0302

Gnomad4 AMR AF: 0.0944

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.124

Alfa AF: 0.153 Hom.: 2717

Bravo AF: 0.116

Asia WGS AF: 0.287 AC: 998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.6
Dann	Benign	0.44

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: rs3788964; hg19: chr2-163207480;