16-67483276-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.464

Publications

16 publications found
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 id 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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AGRPNM_001138.2 linkc.123G>A p.Glu41Glu synonymous_variant Exon 2 of 4 ENST00000290953.3 NP_001129.1 O00253C6SUN5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AGRPENST00000290953.3 linkc.123G>A p.Glu41Glu synonymous_variant Exon 2 of 4 1 NM_001138.2 ENSP00000290953.3 O00253

Frequencies

GnomAD3 genomes
AF:
0.100
AC:
15228
AN:
152122
Hom.:
1356
Cov.:
33
show subpopulations
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
show subpopulations
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
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.472
Heterozygous variant carriers
0
3188
6375
9563
12750
15938
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
1948
3896
5844
7792
9740
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.100
AC:
15278
AN:
152238
Hom.:
1366
Cov.:
33
AF XY:
0.0980
AC XY:
7297
AN XY:
74432
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
0
620
1239
1859
2478
3098
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
156
312
468
624
780
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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
LINK: link

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 v4.3

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

Publications

Other links and lift over

dbSNP: rs34123523; hg19: chr16-67517179; COSMIC: COSV52098655; COSMIC: COSV52098655; API