Genetic Variant CARTPT:c.*126C>A (chr5-71720741-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004291.4(CARTPT):c.*126C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 750,350 control chromosomes in the GnomAD database, including 508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 352 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 156 hom. )

Consequence

CARTPT
NM_004291.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0290

Publications

1 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

inherited obesity
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

CARTPT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 5-71720741-C-A is Benign according to our data. Variant chr5-71720741-C-A is described in ClinVar as Benign. ClinVar VariationId is 1224262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004291.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARTPT	NM_004291.4	MANE Select	c.*126C>A		3_prime_UTR	Exon 3 of 3	NP_004282.1	Q16568

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARTPT	ENST00000296777.5	TSL:1 MANE Select	c.*126C>A		3_prime_UTR	Exon 3 of 3	ENSP00000296777.4	Q16568
	CARTPT	ENST00000513096.1	TSL:2	n.619C>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0363

AC:

5516

AN:

152150

Hom.:

350

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0140

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0315

GnomAD4 exome

AF:

0.00463

AC:

2771

AN:

598082

Hom.:

156

Cov.:

AF XY:

0.00365

AC XY:

1171

AN XY:

320812

show subpopulations

African (AFR)

AF:

0.129

AC:

2074

AN:

16140

American (AMR)

AF:

0.00732

AC:

243

AN:

33200

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19852

East Asian (EAS)

AF:

0.00

AC:

AN:

32034

South Asian (SAS)

AF:

0.000420

AC:

AN:

61864

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44664

Middle Eastern (MID)

AF:

0.00661

AC:

AN:

4086

European-Non Finnish (NFE)

AF:

0.000251

AC:

AN:

354684

Other (OTH)

AF:

0.00989

AC:

312

AN:

31558

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

137

275

412

550

687

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0363

AC:

5526

AN:

152268

Hom.:

352

Cov.:

AF XY:

0.0348

AC XY:

2594

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.126

AC:

5222

AN:

41526

American (AMR)

AF:

0.0139

AC:

213

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

68036

Other (OTH)

AF:

0.0312

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

245

490

734

979

1224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0262

Hom.:

Bravo

AF:

0.0423

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

0.029

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over