rs1790733

Positions:

• chr11-67418529-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.529

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 (HGNC:):

ACMG classification

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	Protein	UniProt
CARNS1	NM_001166222.2	c.364+9A>G		intron_variant		ENST00000687366.1	NP_001159694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARNS1	ENST00000687366.1	c.364+9A>G		intron_variant			NM_001166222.2	ENSP00000510668.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43363 AN: 151898 Hom.: 12099 Cov.: 33

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

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.: 31 AF XY: 0.0980 AC XY: 66348 AN XY: 677254

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.: 33 AF XY: 0.283 AC XY: 21023 AN XY: 74292

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	13
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

Other links and lift over

dbSNP: rs1790733; hg19: chr11-67186000; COSMIC: COSV57130945; COSMIC: COSV57130945;