2-162353833-C-T

Variant names:

• chr2-162353833-C-T
• rs7587426
• NM_012198.5:c.262+1426C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012198.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCA	NM_012198.5	MANE Select	c.262+1426C>T		intron	N/A	NP_036330.1
	GCA	NM_001330268.1		c.340+1426C>T		intron	N/A	NP_001317197.1
	GCA	NM_001330265.1		c.307+1426C>T		intron	N/A	NP_001317194.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCA	ENST00000437150.7	TSL:1 MANE Select	c.262+1426C>T		intron	N/A	ENSP00000394842.2
	GCA	ENST00000233612.8	TSL:2	c.205+1426C>T		intron	N/A	ENSP00000233612.4
	GCA	ENST00000446271.5	TSL:5	c.340+1426C>T		intron	N/A	ENSP00000393218.1

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

African (AFR) AF: 0.186 AC: 7731 AN: 41460

American (AMR) AF: 0.379 AC: 5792 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1408 AN: 3468

East Asian (EAS) AF: 0.0153 AC: 79 AN: 5160

South Asian (SAS) AF: 0.363 AC: 1749 AN: 4822

European-Finnish (FIN) AF: 0.427 AC: 4501 AN: 10540

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 35987 AN: 67950

Other (OTH) AF: 0.414 AC: 871 AN: 2106

Alfa AF: 0.495 Hom.: 18611

Bravo AF: 0.369

Asia WGS AF: 0.189 AC: 658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.65
PhyloP100		0.053
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: rs7587426; hg19: chr2-163210343;