16-67483276-C-T

Variant names:

• chr16-67483276-C-T
• rs34123523
• NM_001138.2:c.123G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001138.2(AGRP):​c.123G>A​(p.Glu41Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0548 in 1,585,708 control chromosomes in the GnomAD database, including 4,162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1366 hom., cov: 33)
  • Exomes 𝑓: 0.050 (2796 hom.)
• Consequence: AGRP NM_001138.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.464
• Publications: 16 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 16-67483276-C-T is Benign according to our data. Variant chr16-67483276-C-T is described in ClinVar as Benign. ClinVar VariationId is 1280192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.464 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

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.123G>A	p.Glu41Glu	synonymous	Exon 2 of 4	NP_001129.1
	ATP6V0D1-DT	NR_184225.1		n.127-834C>T		intron	N/A
	ATP6V0D1-DT	NR_184226.1		n.127-834C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGRP	ENST00000290953.3	TSL:1 MANE Select	c.123G>A	p.Glu41Glu	synonymous	Exon 2 of 4	ENSP00000290953.3
	ATP6V0D1-DT	ENST00000602596.1	TSL:2	n.137-834C>T		intron	N/A
	ATP6V0D1-DT	ENST00000635000.1	TSL:5	n.114-834C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15228 AN: 152122 Hom.: 1356 Cov.: 33

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0641

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0726

Gnomad FIN AF: 0.0374

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0426

Gnomad OTH AF: 0.0957

GnomAD2 exomes AF: 0.0582 AC: 12582 AN: 216048 AF XY: 0.0568

Gnomad AFR exome AF: 0.246

Gnomad AMR exome AF: 0.0389

Gnomad ASJ exome AF: 0.0611

Gnomad EAS exome AF: 0.00256

Gnomad FIN exome AF: 0.0378

Gnomad NFE exome AF: 0.0441

Gnomad OTH exome AF: 0.0549

GnomAD4 exome AF: 0.0499 AC: 71557 AN: 1433470 Hom.: 2796 Cov.: 35 AF XY: 0.0500 AC XY: 35531 AN XY: 710872

African (AFR) AF: 0.256 AC: 8378 AN: 32674

American (AMR) AF: 0.0412 AC: 1689 AN: 40956

Ashkenazi Jewish (ASJ) AF: 0.0625 AC: 1511 AN: 24186

East Asian (EAS) AF: 0.00168 AC: 66 AN: 39258

South Asian (SAS) AF: 0.0768 AC: 6309 AN: 82144

European-Finnish (FIN) AF: 0.0414 AC: 2138 AN: 51658

Middle Eastern (MID) AF: 0.113 AC: 545 AN: 4824

European-Non Finnish (NFE) AF: 0.0429 AC: 47153 AN: 1098800

Other (OTH) AF: 0.0639 AC: 3768 AN: 58970

GnomAD4 genome AF: 0.100 AC: 15278 AN: 152238 Hom.: 1366 Cov.: 33 AF XY: 0.0980 AC XY: 7297 AN XY: 74432

African (AFR) AF: 0.244 AC: 10125 AN: 41504

American (AMR) AF: 0.0640 AC: 979 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0579 AC: 201 AN: 3470

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5180

South Asian (SAS) AF: 0.0722 AC: 349 AN: 4832

European-Finnish (FIN) AF: 0.0374 AC: 397 AN: 10618

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.0427 AC: 2902 AN: 68012

Other (OTH) AF: 0.0952 AC: 201 AN: 2112

Alfa AF: 0.0620 Hom.: 283

Bravo AF: 0.106

Asia WGS AF: 0.0600 AC: 208 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	5.3
DANN	Benign	0.70
PhyloP100		-0.46
PromoterAI		0.038	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: rs34123523; hg19: chr16-67517179; COSMIC: COSV52098655; COSMIC: COSV52098655;