2-162368011-A-G

Position:

• chr2-162368011-A-G

Variant summary

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

The ENST00000414723.1(GCA):​c.366-3295A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 151,754 control chromosomes in the GnomAD database, including 20,315 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 0.49 (20315 hom., cov: 31)
• Consequence: GCA ENST00000414723.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936

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 (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCA	XM_005246446.4	c.628-3295A>G		intron_variant			XP_005246503.1
GCA	XM_006712398.5	c.706-3295A>G		intron_variant			XP_006712461.1
GCA	XM_006712400.5	c.673-3295A>G		intron_variant			XP_006712463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCA	ENST00000414723.1	c.366-3295A>G		intron_variant		3		ENSP00000408620

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74450 AN: 151636 Hom.: 20267 Cov.: 31

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.491 AC: 74556 AN: 151754 Hom.: 20315 Cov.: 31 AF XY: 0.496 AC XY: 36756 AN XY: 74160

Gnomad4 AFR AF: 0.706

Gnomad4 AMR AF: 0.471

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.829

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.462

Alfa AF: 0.379 Hom.: 23154

Bravo AF: 0.509

Asia WGS AF: 0.624 AC: 2166 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	1.0
DANN	Benign	0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs984971; hg19: chr2-163224521;