chr16-67483152-G-A

Variant names:

• chr16-67483152-G-A
• rs11575892
• NM_001138.2:c.131-42C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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:55268): (ATP6V0D1 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 47 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001138.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGRP	NM_001138.2	MANE Select	c.131-42C>T		intron	N/A	NP_001129.1
	ATP6V0D1-DT	NR_184225.1		n.127-958G>A		intron	N/A
	ATP6V0D1-DT	NR_184226.1		n.127-958G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGRP	ENST00000290953.3	TSL:1 MANE Select	c.131-42C>T		intron	N/A	ENSP00000290953.3
	ATP6V0D1-DT	ENST00000602596.1	TSL:2	n.137-958G>A		intron	N/A
	ATP6V0D1-DT	ENST00000635000.1	TSL:5	n.114-958G>A		intron	N/A

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

GnomAD2 exomes AF: 0.0244 AC: 6083 AN: 249414 AF XY: 0.0252

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 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

African (AFR) AF: 0.0262 AC: 875 AN: 33430

American (AMR) AF: 0.0121 AC: 541 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 437 AN: 26098

East Asian (EAS) AF: 0.00822 AC: 326 AN: 39680

South Asian (SAS) AF: 0.0293 AC: 2525 AN: 86192

European-Finnish (FIN) AF: 0.0114 AC: 606 AN: 53252

Middle Eastern (MID) AF: 0.0294 AC: 169 AN: 5754

European-Non Finnish (NFE) AF: 0.0326 AC: 36243 AN: 1110278

Other (OTH) AF: 0.0273 AC: 1644 AN: 60300

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

African (AFR) AF: 0.0267 AC: 1110 AN: 41576

American (AMR) AF: 0.0151 AC: 231 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3470

East Asian (EAS) AF: 0.00947 AC: 49 AN: 5176

South Asian (SAS) AF: 0.0308 AC: 149 AN: 4830

European-Finnish (FIN) AF: 0.00894 AC: 95 AN: 10626

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0300 AC: 2039 AN: 68000

Other (OTH) AF: 0.0293 AC: 62 AN: 2116

Alfa AF: 0.0276 Hom.: 10

Bravo AF: 0.0254

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.0
DANN	Benign	0.61
PhyloP100		-0.38
PromoterAI		0.015	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: rs11575892; hg19: chr16-67517055;