rs34354539

Positions:

• chr11-10307200-T-TC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001124.3(ADM):​c.*563dupC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.48 (18286 hom., cov: 0)
  • Exomes 𝑓: 0.52 (59 hom.)
• Consequence: ADM NM_001124.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADM	NM_001124.3	c.*563dupC		3_prime_UTR_variant	4/4	ENST00000278175.10	NP_001115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADM	ENST00000278175.10	c.*563dupC		3_prime_UTR_variant	4/4	1	NM_001124.3	ENSP00000278175.5
ADM	ENST00000528655.5	c.*563dupC		3_prime_UTR_variant	3/3	1		ENSP00000436607.1
ADM	ENST00000534464.1	c.*563dupC		3_prime_UTR_variant	3/3	2		ENSP00000431438.1
ADM	ENST00000530439.1	c.*563dupC		3_prime_UTR_variant	2/2	2		ENSP00000436837.1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73459 AN: 151904 Hom.: 18255 Cov.: 0

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.482

GnomAD4 exome AF: 0.523 AC: 231 AN: 442 Hom.: 59 Cov.: 0 AF XY: 0.522 AC XY: 141 AN XY: 270

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.525

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.484 AC: 73553 AN: 152022 Hom.: 18286 Cov.: 0 AF XY: 0.485 AC XY: 36038 AN XY: 74314

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.483

Alfa AF: 0.508 Hom.: 2456

Bravo AF: 0.466

Asia WGS AF: 0.373 AC: 1297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs34354539; hg19: chr11-10328747;