rs2793823

chr1-119895095-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_021794.4(ADAM30):c.1242C>T(p.Asp414=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,613,932 control chromosomes in the GnomAD database, including 31,295 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (8970 hom., cov: 32)
  • Exomes 𝑓: 0.15 (22325 hom.)
• Consequence: ADAM30 NM_021794.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.567

Genes affected

ADAM30 (HGNC:208): (ADAM metallopeptidase domain 30) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. This gene is testis-specific and contains a polymorphic region, resulting in isoforms with varying numbers of C-terminal repeats. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-0.567 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM30	NM_021794.4	c.1242C>T	p.Asp414=	synonymous_variant	1/1	ENST00000369400.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM30	ENST00000369400.2	c.1242C>T	p.Asp414=	synonymous_variant	1/1		NM_021794.4	P1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41100 AN: 151994 Hom.: 8942 Cov.: 32

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0958

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.237

GnomAD3 exomes AF: 0.188 AC: 47325 AN: 251240 Hom.: 6647 AF XY: 0.185 AC XY: 25070 AN XY: 135810

Gnomad AFR exome AF: 0.618

Gnomad AMR exome AF: 0.187

Gnomad ASJ exome AF: 0.117

Gnomad EAS exome AF: 0.0995

Gnomad SAS exome AF: 0.295

Gnomad FIN exome AF: 0.177

Gnomad NFE exome AF: 0.123

Gnomad OTH exome AF: 0.162

GnomAD4 exome AF: 0.151 AC: 220172 AN: 1461820 Hom.: 22325 Cov.: 33 AF XY: 0.153 AC XY: 111451 AN XY: 727216

Gnomad4 AFR exome AF: 0.622

Gnomad4 AMR exome AF: 0.186

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.0672

Gnomad4 SAS exome AF: 0.288

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.173

GnomAD4 genome AF: 0.271 AC: 41177 AN: 152112 Hom.: 8970 Cov.: 32 AF XY: 0.271 AC XY: 20143 AN XY: 74362

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0955

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.245

Alfa AF: 0.161 Hom.: 5245

Bravo AF: 0.281

Asia WGS AF: 0.299 AC: 1038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.38
Dann	Benign	0.34

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: rs2793823; hg19: chr1-120437718; COSMIC: COSV65560549;