rs5005

chr11-10306000-C-Gchr11-10306000-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001124.3(ADM):c.150C>G(p.Ser50Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00601 in 1,613,964 control chromosomes in the GnomAD database, including 204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.021 (81 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (123 hom.)
• Consequence: ADM NM_001124.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.915

Genes affected

ADM (HGNC:259): (adrenomedullin) The protein encoded by this gene is a preprohormone which is cleaved to form two biologically active peptides, adrenomedullin and proadrenomedullin N-terminal 20 peptide. Adrenomedullin is a 52 aa peptide with several functions, including vasodilation, regulation of hormone secretion, promotion of angiogenesis, and antimicrobial activity. The antimicrobial activity is antibacterial, as the peptide has been shown to kill E. coli and S. aureus at low concentration. [provided by RefSeq, Aug 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022379458).
• BP6: Variant 11-10306000-C-G is Benign according to our data. Variant chr11-10306000-C-G is described in ClinVar as [Benign]. Clinvar id is 779135.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-10306000-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADM	NM_001124.3	c.150C>G	p.Ser50Arg	missense_variant	3/4	ENST00000278175.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADM	ENST00000278175.10	c.150C>G	p.Ser50Arg	missense_variant	3/4	1	NM_001124.3	P1

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3170 AN: 152056 Hom.: 81 Cov.: 32

Gnomad AFR AF: 0.0627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00265

Gnomad OTH AF: 0.0258

GnomAD3 exomes AF: 0.00919 AC: 2307 AN: 251132 Hom.: 42 AF XY: 0.00786 AC XY: 1068 AN XY: 135798

Gnomad AFR exome AF: 0.0704

Gnomad AMR exome AF: 0.00954

Gnomad ASJ exome AF: 0.0402

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000621

Gnomad FIN exome AF: 0.0000929

Gnomad NFE exome AF: 0.00299

Gnomad OTH exome AF: 0.0111

GnomAD4 exome AF: 0.00447 AC: 6532 AN: 1461790 Hom.: 123 Cov.: 32 AF XY: 0.00429 AC XY: 3118 AN XY: 727206

Gnomad4 AFR exome AF: 0.0658

Gnomad4 AMR exome AF: 0.0102

Gnomad4 ASJ exome AF: 0.0376

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000638

Gnomad4 FIN exome AF: 0.0000938

Gnomad4 NFE exome AF: 0.00183

Gnomad4 OTH exome AF: 0.0104

GnomAD4 genome AF: 0.0209 AC: 3175 AN: 152174 Hom.: 81 Cov.: 32 AF XY: 0.0202 AC XY: 1499 AN XY: 74388

Gnomad4 AFR AF: 0.0627

Gnomad4 AMR AF: 0.0139

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00265

Gnomad4 OTH AF: 0.0255

Alfa AF: 0.00599 Hom.: 14

Bravo AF: 0.0243

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.0595 AC: 262

ESP6500EA AF: 0.00338 AC: 29

ExAC AF: 0.00969 AC: 1177

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.00409

EpiControl AF: 0.00563

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.22	T;T;T;T;T;T;T
Eigen	Benign	0.18
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.39	N
MetaRNN	Benign	0.0022	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.;.;M;.;M;.
MutationTaster	Benign	0.93	D;D;D;D;N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.5	N;N;D;N;D;N;D
REVEL	Benign	0.074
Sift	Benign	0.13	T;D;D;T;D;T;D
Sift4G	Benign	0.43	T;D;T;T;D;T;T
Polyphen		0.96	D;.;.;D;.;D;.
Vest4		0.20
MutPred		0.25		Loss of phosphorylation at S50 (P = 0.0138);.;Loss of phosphorylation at S50 (P = 0.0138);Loss of phosphorylation at S50 (P = 0.0138);Loss of phosphorylation at S50 (P = 0.0138);Loss of phosphorylation at S50 (P = 0.0138);Loss of phosphorylation at S50 (P = 0.0138);
MVP		0.42
MPC		0.62
ClinPred		0.022	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.53

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: rs5005; hg19: chr11-10327547;