Variant chr2-162352383-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000437150.7(GCA):c.238T>G(p.Ser80Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,582,658 control chromosomes in the GnomAD database, including 13,337 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.096 ( 922 hom., cov: 32)

Exomes 𝑓: 0.12 ( 12415 hom. )

Consequence

GCA
ENST00000437150.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.08

Variant links:

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]

GCA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014909804).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCA	NM_012198.5 linkuse as main transcript	c.238T>G	p.Ser80Ala	missense_variant	3/8	ENST00000437150.7	NP_036330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCA	ENST00000437150.7 linkuse as main transcript	c.238T>G	p.Ser80Ala	missense_variant	3/8	1	NM_012198.5	ENSP00000394842	P1

Frequencies

GnomAD3 genomes

AF:

0.0957

AC:

14551

AN:

152098

Hom.:

922

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0262

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0577

Gnomad FIN

AF:

0.0987

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.121

GnomAD3 exomes

AF:

0.106

AC:

26427

AN:

250464

Hom.:

1902

AF XY:

0.109

AC XY:

14695

AN XY:

135386

show subpopulations

Gnomad AFR exome

AF:

0.0241

Gnomad AMR exome

AF:

0.0681

Gnomad ASJ exome

AF:

0.227

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0583

Gnomad FIN exome

AF:

0.102

Gnomad NFE exome

AF:

0.147

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.123

AC:

176333

AN:

1430442

Hom.:

12415

Cov.:

AF XY:

0.123

AC XY:

87544

AN XY:

713640

show subpopulations

Gnomad4 AFR exome

AF:

0.0248

Gnomad4 AMR exome

AF:

0.0718

Gnomad4 ASJ exome

AF:

0.223

Gnomad4 EAS exome

AF:

0.000355

Gnomad4 SAS exome

AF:

0.0588

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.136

Gnomad4 OTH exome

AF:

0.126

GnomAD4 genome

AF:

0.0956

AC:

14547

AN:

152216

Hom.:

922

Cov.:

AF XY:

0.0940

AC XY:

6994

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0261

Gnomad4 AMR

AF:

0.103

Gnomad4 ASJ

AF:

0.218

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.0579

Gnomad4 FIN

AF:

0.0987

Gnomad4 NFE

AF:

0.138

Gnomad4 OTH

AF:

0.120

Alfa

AF:

0.135

Hom.:

3800

Bravo

AF:

0.0947

TwinsUK

AF:

0.142

AC:

525

ALSPAC

AF:

0.145

AC:

559

ESP6500AA

AF:

0.0318

AC:

140

ESP6500EA

AF:

0.145

AC:

1247

ExAC

AF:

0.107

AC:

12963

Asia WGS

AF:

0.0320

AC:

113

AN:

3474

EpiCase

AF:

0.155

EpiControl

AF:

0.160

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

T;T;T;.;.

Eigen

Benign

-0.17

Eigen_PC

Benign

0.010

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.53

T;T;T;T;T

MetaRNN

Benign

0.0015

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

.;.;L;.;.

MutationTaster

Benign

0.0091

P;P;P

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.8

N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.32

T;T;T;T;T

Sift4G

Benign

0.14

T;T;T;T;T

Polyphen

0.0010

.;.;B;.;.

Vest4

0.082, 0.075, 0.053

MPC

0.094

ClinPred

0.010

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.30

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over