Variant chr11-67418529-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001166222.2(CARNS1):c.364+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,526,254 control chromosomes in the GnomAD database, including 29,160 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 0.29 ( 12144 hom., cov: 33)

Exomes 𝑓: 0.10 ( 17016 hom. )

Consequence

CARNS1
NM_001166222.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.529

Variant links:

Genes affected

CARNS1 (HGNC:29268): (carnosine synthase 1) CARNS1 (EC 6.3.2.11), a member of the ATP-grasp family of ATPases, catalyzes the formation of carnosine (beta-alanyl-L-histidine) and homocarnosine (gamma-aminobutyryl-L-histidine), which are found mainly in skeletal muscle and the central nervous system, respectively (Drozak et al., 2010 [PubMed 20097752]).[supplied by OMIM, Apr 2010]

CARNS1 links:

PPP1CA (HGNC:9281): (protein phosphatase 1 catalytic subunit alpha) The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). This broadly expressed gene encodes the alpha subunit of the PP1 complex that associates with over 200 regulatory proteins to form holoenzymes which dephosphorylate their biological targets with high specificity. PP1 is a serine/threonine specific protein phosphatase known to be involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Increased PP1 activity has been observed in the end stage of heart failure. Studies suggest that PP1 is an important regulator of cardiac function and that PP1 deregulation is implicated in diabetes and multiple types of cancer. Three alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2020]

PPP1CA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARNS1	NM_001166222.2 linkuse as main transcript	c.364+9A>G		intron_variant		ENST00000687366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARNS1	ENST00000687366.1 linkuse as main transcript	c.364+9A>G		intron_variant			NM_001166222.2	P2	A5YM72-5

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43363

AN:

151898

Hom.:

12099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.715

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.0602

Gnomad EAS

AF:

0.253

Gnomad SAS

AF:

0.0677

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.119

Gnomad NFE

AF:

0.0774

Gnomad OTH

AF:

0.230

GnomAD3 exomes

AF:

0.183

AC:

24841

AN:

135928

Hom.:

4901

AF XY:

0.157

AC XY:

11416

AN XY:

72866

show subpopulations

Gnomad AFR exome

AF:

0.727

Gnomad AMR exome

AF:

0.428

Gnomad ASJ exome

AF:

0.0587

Gnomad EAS exome

AF:

0.253

Gnomad SAS exome

AF:

0.0610

Gnomad FIN exome

AF:

0.106

Gnomad NFE exome

AF:

0.0724

Gnomad OTH exome

AF:

0.154

GnomAD4 exome

AF:

0.102

AC:

140472

AN:

1374236

Hom.:

17016

Cov.:

AF XY:

0.0980

AC XY:

66348

AN XY:

677254

show subpopulations

Gnomad4 AFR exome

AF:

0.738

Gnomad4 AMR exome

AF:

0.418

Gnomad4 ASJ exome

AF:

0.0619

Gnomad4 EAS exome

AF:

0.250

Gnomad4 SAS exome

AF:

0.0646

Gnomad4 FIN exome

AF:

0.120

Gnomad4 NFE exome

AF:

0.0705

Gnomad4 OTH exome

AF:

0.132

GnomAD4 genome

AF:

0.286

AC:

43471

AN:

152018

Hom.:

12144

Cov.:

AF XY:

0.283

AC XY:

21023

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.715

Gnomad4 AMR

AF:

0.317

Gnomad4 ASJ

AF:

0.0602

Gnomad4 EAS

AF:

0.253

Gnomad4 SAS

AF:

0.0682

Gnomad4 FIN

AF:

0.125

Gnomad4 NFE

AF:

0.0774

Gnomad4 OTH

AF:

0.229

Alfa

AF:

0.124

Hom.:

1450

Bravo

AF:

0.326

Asia WGS

AF:

0.226

AC:

785

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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