Variant 19-12938676-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_004343.4(CALR):c.-4C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,607,766 control chromosomes in the GnomAD database, including 46 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 36 hom. )

Consequence

CALR
NM_004343.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.115

Variant links:

Genes affected

CALR (HGNC:1455): (calreticulin) Calreticulin is a highly conserved chaperone protein which resides primarily in the endoplasmic reticulum, and is involved in a variety of cellular processes, among them, cell adhesion. Additionally, it functions in protein folding quality control and calcium homeostasis. Calreticulin is also found in the nucleus, suggesting that it may have a role in transcription regulation. Systemic lupus erythematosus is associated with increased autoantibody titers against calreticulin. Recurrent mutations in calreticulin have been linked to various neoplasms, including the myeloproliferative type.[provided by RefSeq, May 2020]

CALR links:

CALR (HGNC:):

CALR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 19-12938676-C-T is Benign according to our data. Variant chr19-12938676-C-T is described in ClinVar as [Benign]. Clinvar id is 1269519.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00198 (301/152368) while in subpopulation EAS AF= 0.0521 (270/5180). AF 95% confidence interval is 0.047. There are 10 homozygotes in gnomad4. There are 184 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 301 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALR	NM_004343.4 linkuse as main transcript	c.-4C>T		5_prime_UTR_premature_start_codon_gain_variant	1/9	ENST00000316448.10	NP_004334.1	P27797V9HW88
CALR	NM_004343.4 linkuse as main transcript	c.-4C>T		5_prime_UTR_variant	1/9	ENST00000316448.10	NP_004334.1	P27797V9HW88

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALR	ENST00000316448 linkuse as main transcript	c.-4C>T		5_prime_UTR_premature_start_codon_gain_variant	1/9	1	NM_004343.4	ENSP00000320866.4		P27797
CALR	ENST00000316448 linkuse as main transcript	c.-4C>T		5_prime_UTR_variant	1/9	1	NM_004343.4	ENSP00000320866.4		P27797

Frequencies

GnomAD3 genomes

AF:

0.00198

AC:

302

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.0520

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00458

AC:

1065

AN:

232634

Hom.:

AF XY:

0.00438

AC XY:

561

AN XY:

128084

show subpopulations

Gnomad AFR exome

AF:

0.000146

Gnomad AMR exome

AF:

0.000178

Gnomad ASJ exome

AF:

0.00550

Gnomad EAS exome

AF:

0.0558

Gnomad SAS exome

AF:

0.000775

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000680

Gnomad OTH exome

AF:

0.00122

GnomAD4 exome

AF:

0.00132

AC:

1928

AN:

1455398

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

982

AN XY:

723650

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000678

Gnomad4 ASJ exome

AF:

0.00393

Gnomad4 EAS exome

AF:

0.0399

Gnomad4 SAS exome

AF:

0.000784

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.00250

GnomAD4 genome

AF:

0.00198

AC:

301

AN:

152368

Hom.:

Cov.:

AF XY:

0.00247

AC XY:

184

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.0521

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000914

Hom.:

Bravo

AF:

0.00298

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Benign

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over