rs2239670

Positions:

• chr5-71719676-A-G
• chr5-71719676-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004291.4(CARTPT):​c.160-204A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 743,230 control chromosomes in the GnomAD database, including 271,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.86 (56969 hom., cov: 31)
  • Exomes 𝑓: 0.85 (214729 hom.)
• Consequence: CARTPT NM_004291.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00700

Genes affected

CARTPT (HGNC:24323): (CART prepropeptide) This gene encodes a preproprotein that is proteolytically processed to generate multiple biologically active peptides. These peptides play a role in appetite, energy balance, maintenance of body weight, reward and addiction, and the stress response. Expression of a similar gene transcript in rodents is upregulated following administration of cocaine and amphetamine. Mutations in this gene are associated with susceptibility to obesity in humans. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-71719676-A-G is Benign according to our data. Variant chr5-71719676-A-G is described in ClinVar as [Benign]. Clinvar id is 1183143.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARTPT	NM_004291.4	c.160-204A>G		intron_variant		ENST00000296777.5	NP_004282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARTPT	ENST00000296777.5	c.160-204A>G		intron_variant		1	NM_004291.4	ENSP00000296777	P1
CARTPT	ENST00000513096.1	n.98A>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.865 AC: 131446 AN: 152044 Hom.: 56913 Cov.: 31

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.936

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.806

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.867

Gnomad OTH AF: 0.856

GnomAD4 exome AF: 0.851 AC: 502964 AN: 591066 Hom.: 214729 Cov.: 7 AF XY: 0.848 AC XY: 264578 AN XY: 311840

Gnomad4 AFR exome AF: 0.897

Gnomad4 AMR exome AF: 0.847

Gnomad4 ASJ exome AF: 0.849

Gnomad4 EAS exome AF: 0.707

Gnomad4 SAS exome AF: 0.810

Gnomad4 FIN exome AF: 0.829

Gnomad4 NFE exome AF: 0.871

Gnomad4 OTH exome AF: 0.848

GnomAD4 genome AF: 0.865 AC: 131555 AN: 152164 Hom.: 56969 Cov.: 31 AF XY: 0.859 AC XY: 63892 AN XY: 74358

Gnomad4 AFR AF: 0.894

Gnomad4 AMR AF: 0.871

Gnomad4 ASJ AF: 0.858

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.807

Gnomad4 FIN AF: 0.819

Gnomad4 NFE AF: 0.867

Gnomad4 OTH AF: 0.857

Alfa AF: 0.861 Hom.: 42768

Bravo AF: 0.865

Asia WGS AF: 0.780 AC: 2715 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.5
DANN	Benign	0.59

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

Other links and lift over

dbSNP: rs2239670; hg19: chr5-71015503; COSMIC: COSV57115778;