rs11575892

Positions:

• chr16-67483152-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001138.2(AGRP):​c.131-42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0293 in 1,611,970 control chromosomes in the GnomAD database, including 759 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.025 (47 hom., cov: 33)
  • Exomes 𝑓: 0.030 (712 hom.)
• Consequence: AGRP NM_001138.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376

Genes affected

AGRP (HGNC:330): (agouti related neuropeptide) This gene encodes an antagonist of the melanocortin-3 and melanocortin-4 receptor. It appears to regulate hypothalamic control of feeding behavior via melanocortin receptor and/or intracellular calcium regulation, and thus plays a role in weight homeostasis. Mutations in this gene have been associated with late on-set obesity. [provided by RefSeq, Dec 2009]

ATP6V0D1-DT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0251 (3823/152306) while in subpopulation SAS AF= 0.0308 (149/4830). AF 95% confidence interval is 0.0289. There are 47 homozygotes in gnomad4. There are 1800 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGRP	NM_001138.2	c.131-42C>T		intron_variant		ENST00000290953.3	NP_001129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGRP	ENST00000290953.3	c.131-42C>T		intron_variant		1	NM_001138.2	ENSP00000290953.3

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 3818 AN: 152188 Hom.: 47 Cov.: 33

Gnomad AFR AF: 0.0267

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00925

Gnomad SAS AF: 0.0308

Gnomad FIN AF: 0.00894

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0300

Gnomad OTH AF: 0.0277

GnomAD3 exomes AF: 0.0244 AC: 6083 AN: 249414 Hom.: 73 AF XY: 0.0252 AC XY: 3407 AN XY: 135234

Gnomad AFR exome AF: 0.0265

Gnomad AMR exome AF: 0.0112

Gnomad ASJ exome AF: 0.0172

Gnomad EAS exome AF: 0.00687

Gnomad SAS exome AF: 0.0309

Gnomad FIN exome AF: 0.0103

Gnomad NFE exome AF: 0.0327

Gnomad OTH exome AF: 0.0205

GnomAD4 exome AF: 0.0297 AC: 43366 AN: 1459664 Hom.: 712 Cov.: 31 AF XY: 0.0298 AC XY: 21639 AN XY: 726208

Gnomad4 AFR exome AF: 0.0262

Gnomad4 AMR exome AF: 0.0121

Gnomad4 ASJ exome AF: 0.0167

Gnomad4 EAS exome AF: 0.00822

Gnomad4 SAS exome AF: 0.0293

Gnomad4 FIN exome AF: 0.0114

Gnomad4 NFE exome AF: 0.0326

Gnomad4 OTH exome AF: 0.0273

GnomAD4 genome AF: 0.0251 AC: 3823 AN: 152306 Hom.: 47 Cov.: 33 AF XY: 0.0242 AC XY: 1800 AN XY: 74474

Gnomad4 AFR AF: 0.0267

Gnomad4 AMR AF: 0.0151

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.00947

Gnomad4 SAS AF: 0.0308

Gnomad4 FIN AF: 0.00894

Gnomad4 NFE AF: 0.0300

Gnomad4 OTH AF: 0.0293

Alfa AF: 0.0280 Hom.: 9

Bravo AF: 0.0254

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.0
DANN	Benign	0.61

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: rs11575892; hg19: chr16-67517055;