NM_004291.4:c.160-204A>G

Variant names:

• chr5-71719676-A-G
• rs2239670
• NM_004291.4:c.160-204A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
CARTPT	NM_004291.4	c.160-204A>G		intron_variant	Intron 1 of 2	ENST00000296777.5	NP_004282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARTPT	ENST00000296777.5	c.160-204A>G		intron_variant	Intron 1 of 2	1	NM_004291.4	ENSP00000296777.4
CARTPT	ENST00000513096.1	n.98A>G		non_coding_transcript_exon_variant	Exon 1 of 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

African (AFR) AF: 0.897 AC: 14545 AN: 16216

American (AMR) AF: 0.847 AC: 26519 AN: 31312

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 14765 AN: 17396

East Asian (EAS) AF: 0.707 AC: 22681 AN: 32088

South Asian (SAS) AF: 0.810 AC: 45556 AN: 56250

European-Finnish (FIN) AF: 0.829 AC: 26750 AN: 32256

Middle Eastern (MID) AF: 0.786 AC: 1932 AN: 2458

European-Non Finnish (NFE) AF: 0.871 AC: 323575 AN: 371688

Other (OTH) AF: 0.848 AC: 26641 AN: 31402

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

African (AFR) AF: 0.894 AC: 37159 AN: 41544

American (AMR) AF: 0.871 AC: 13334 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 2976 AN: 3468

East Asian (EAS) AF: 0.719 AC: 3682 AN: 5120

South Asian (SAS) AF: 0.807 AC: 3884 AN: 4812

European-Finnish (FIN) AF: 0.819 AC: 8673 AN: 10592

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.867 AC: 58950 AN: 68002

Other (OTH) AF: 0.857 AC: 1811 AN: 2114

Alfa AF: 0.863 Hom.: 58013

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.5
DANN	Benign	0.59
PhyloP100		0.0070
PromoterAI		-0.020	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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