rs5005

Variant names:

• chr11-10306000-C-G
• rs5005
• NM_001124.3:c.150C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-10306000-C-G
• chr11-10306000-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.915
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -20 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 VariationId is 779135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0607 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001124.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADM	NM_001124.3	MANE Select	c.150C>G	p.Ser50Arg	missense	Exon 3 of 4	NP_001115.1	P35318

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADM	ENST00000278175.10	TSL:1 MANE Select	c.150C>G	p.Ser50Arg	missense	Exon 3 of 4	ENSP00000278175.5	P35318
	ADM	ENST00000528655.5	TSL:1	c.150C>G	p.Ser50Arg	missense	Exon 2 of 3	ENSP00000436607.1	P35318
	ADM	ENST00000525063.2	TSL:3	c.150C>G	p.Ser50Arg	missense	Exon 3 of 5	ENSP00000435124.1	P35318

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

GnomAD2 exomes AF: 0.00919 AC: 2307 AN: 251132 AF XY: 0.00786

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 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

African (AFR) AF: 0.0658 AC: 2203 AN: 33480

American (AMR) AF: 0.0102 AC: 456 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0376 AC: 983 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000638 AC: 55 AN: 86258

European-Finnish (FIN) AF: 0.0000938 AC: 5 AN: 53320

Middle Eastern (MID) AF: 0.0293 AC: 169 AN: 5768

European-Non Finnish (NFE) AF: 0.00183 AC: 2032 AN: 1112010

Other (OTH) AF: 0.0104 AC: 629 AN: 60396

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

African (AFR) AF: 0.0627 AC: 2602 AN: 41504

American (AMR) AF: 0.0139 AC: 213 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 112 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5144

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00265 AC: 180 AN: 68012

Other (OTH) AF: 0.0255 AC: 54 AN: 2114

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	0.18
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.92
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.074
Sift	Benign	0.13	T
Sift4G	Benign	0.43	T
Polyphen		0.96	D
Vest4		0.20
MutPred		0.25		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
Mutation Taster		=284/16	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: rs5005; hg19: chr11-10327547;