5-71719624-C-T

Variant names:

• chr5-71719624-C-T
• rs11575893
• NM_004291.4:c.159+172C>T

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.159+172C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 841,580 control chromosomes in the GnomAD database, including 6,089 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1512 hom., cov: 32)
  • Exomes 𝑓: 0.11 (4577 hom.)
• Consequence: CARTPT NM_004291.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.428
• Publications: 11 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: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 5-71719624-C-T is Benign according to our data. Variant chr5-71719624-C-T is described in ClinVar as Benign. ClinVar VariationId is 1250951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 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.159+172C>T		intron	N/A	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.159+172C>T		intron	N/A	ENSP00000296777.4	Q16568
	CARTPT	ENST00000513096.1	TSL:2	n.46C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20177 AN: 151900 Hom.: 1504 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.0573

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.0928

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0896

Gnomad OTH AF: 0.108

GnomAD4 exome AF: 0.107 AC: 73871 AN: 689560 Hom.: 4577 Cov.: 9 AF XY: 0.107 AC XY: 38525 AN XY: 358694

African (AFR) AF: 0.194 AC: 3551 AN: 18318

American (AMR) AF: 0.184 AC: 5867 AN: 31880

Ashkenazi Jewish (ASJ) AF: 0.0844 AC: 1526 AN: 18070

East Asian (EAS) AF: 0.151 AC: 4914 AN: 32520

South Asian (SAS) AF: 0.146 AC: 8508 AN: 58314

European-Finnish (FIN) AF: 0.136 AC: 4489 AN: 32926

Middle Eastern (MID) AF: 0.0773 AC: 269 AN: 3480

European-Non Finnish (NFE) AF: 0.0892 AC: 40988 AN: 459362

Other (OTH) AF: 0.108 AC: 3759 AN: 34690

GnomAD4 genome AF: 0.133 AC: 20207 AN: 152020 Hom.: 1512 Cov.: 32 AF XY: 0.134 AC XY: 9964 AN XY: 74316

African (AFR) AF: 0.197 AC: 8148 AN: 41452

American (AMR) AF: 0.142 AC: 2166 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0928 AC: 322 AN: 3468

East Asian (EAS) AF: 0.171 AC: 881 AN: 5146

South Asian (SAS) AF: 0.154 AC: 740 AN: 4812

European-Finnish (FIN) AF: 0.147 AC: 1557 AN: 10604

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0896 AC: 6086 AN: 67938

Other (OTH) AF: 0.106 AC: 224 AN: 2112

Alfa AF: 0.105 Hom.: 2314

Bravo AF: 0.136

Asia WGS AF: 0.166 AC: 575 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	2.0
DANN	Benign	0.92
PhyloP100		-0.43
PromoterAI		0.00060	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: rs11575893; hg19: chr5-71015451; COSMIC: COSV57115469;