5-71720621-C-G

Position:

• chr5-71720621-C-G

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.*6C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00406 in 1,589,438 control chromosomes in the GnomAD database, including 346 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0065 (30 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (316 hom.)
• Consequence: CARTPT NM_004291.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.17

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]

CARTPT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-71720621-C-G is Benign according to our data. Variant chr5-71720621-C-G is described in ClinVar as [Benign]. Clinvar id is 1175375.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.055 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARTPT	NM_004291.4	c.*6C>G		3_prime_UTR_variant	3/3	ENST00000296777.5	NP_004282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARTPT	ENST00000296777.5	c.*6C>G		3_prime_UTR_variant	3/3	1	NM_004291.4	ENSP00000296777.4
CARTPT	ENST00000513096.1	n.499C>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.00649 AC: 980 AN: 150960 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0581

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00869

Gnomad SAS AF: 0.000215

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00716

GnomAD3 exomes AF: 0.0186 AC: 4087 AN: 219604 Hom.: 243 AF XY: 0.0139 AC XY: 1635 AN XY: 117438

Gnomad AFR exome AF: 0.000566

Gnomad AMR exome AF: 0.122

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0108

Gnomad SAS exome AF: 0.000227

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000923

Gnomad OTH exome AF: 0.0108

GnomAD4 exome AF: 0.00380 AC: 5469 AN: 1438362 Hom.: 316 Cov.: 29 AF XY: 0.00312 AC XY: 2226 AN XY: 714202

Gnomad4 AFR exome AF: 0.000634

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0111

Gnomad4 SAS exome AF: 0.000180

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000584

Gnomad4 OTH exome AF: 0.00273

GnomAD4 genome AF: 0.00651 AC: 983 AN: 151076 Hom.: 30 Cov.: 32 AF XY: 0.00724 AC XY: 534 AN XY: 73756

Gnomad4 AFR AF: 0.000722

Gnomad4 AMR AF: 0.0582

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00870

Gnomad4 SAS AF: 0.000215

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000119

Gnomad4 OTH AF: 0.00709

Alfa AF: 0.000530 Hom.: 0

Bravo AF: 0.0119

Asia WGS AF: 0.00375 AC: 13 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	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.12
DANN	Benign	0.56

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: rs1800926; hg19: chr5-71016448;