chr2-162350970-T-C

Variant names:

• chr2-162350970-T-C
• rs3788964
• NM_012198.5:c.193-1368T>C

Variant summary

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

The NM_001330268.1(GCA):​c.271-1368T>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_001330268.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266
• Publications: 18 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330268.1. 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.193-1368T>C		intron	N/A	NP_036330.1
	GCA	NM_001330268.1		c.271-1368T>C		intron	N/A	NP_001317197.1
	GCA	NM_001330265.1		c.238-1368T>C		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.193-1368T>C		intron	N/A	ENSP00000394842.2
	GCA	ENST00000935560.1		c.193-1347T>C		intron	N/A	ENSP00000605619.1
	GCA	ENST00000935559.1		c.193-1368T>C		intron	N/A	ENSP00000605618.1

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

African (AFR) AF: 0.0302 AC: 1255 AN: 41568

American (AMR) AF: 0.0944 AC: 1444 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 462 AN: 3470

East Asian (EAS) AF: 0.315 AC: 1626 AN: 5158

South Asian (SAS) AF: 0.318 AC: 1536 AN: 4826

European-Finnish (FIN) AF: 0.161 AC: 1699 AN: 10574

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10965 AN: 67960

Other (OTH) AF: 0.124 AC: 262 AN: 2108

Alfa AF: 0.141 Hom.: 3825

Bravo AF: 0.116

Asia WGS AF: 0.287 AC: 998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.44
PhyloP100		0.27
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: rs3788964; hg19: chr2-163207480;