rs7608315

Variant names:

• chr2-162357213-A-C
• rs7608315
• NM_012198.5:c.454+308A>C

Variant summary

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

The NM_012198.5(GCA):​c.454+308A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 151,568 control chromosomes in the GnomAD database, including 31,358 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 0.62 (31358 hom., cov: 31)
• Consequence: GCA NM_012198.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 12 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCA	NM_012198.5	c.454+308A>C		intron_variant	Intron 5 of 7	ENST00000437150.7	NP_036330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCA	ENST00000437150.7	c.454+308A>C		intron_variant	Intron 5 of 7	1	NM_012198.5	ENSP00000394842.2

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93326 AN: 151450 Hom.: 31284 Cov.: 31

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.980

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.617 AC: 93461 AN: 151568 Hom.: 31358 Cov.: 31 AF XY: 0.624 AC XY: 46231 AN XY: 74092

African (AFR) AF: 0.855 AC: 35429 AN: 41414

American (AMR) AF: 0.621 AC: 9421 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2010 AN: 3466

East Asian (EAS) AF: 0.980 AC: 5066 AN: 5170

South Asian (SAS) AF: 0.616 AC: 2965 AN: 4814

European-Finnish (FIN) AF: 0.566 AC: 5980 AN: 10562

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30680 AN: 67652

Other (OTH) AF: 0.583 AC: 1227 AN: 2106

Alfa AF: 0.531 Hom.: 11992

Bravo AF: 0.634

Asia WGS AF: 0.807 AC: 2806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.71
DANN	Benign	0.64
PhyloP100		-1.2
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: rs7608315; hg19: chr2-163213723;