1-119895095-G-A

Variant names:

• chr1-119895095-G-A
• rs2793823
• NM_021794.4:c.1242C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_021794.4(ADAM30):​c.1242C>T​(p.Asp414Asp) 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
• Publications: 29 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021794.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM30	NM_021794.4	MANE Select	c.1242C>T	p.Asp414Asp	synonymous	Exon 1 of 1	NP_068566.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM30	ENST00000369400.2	TSL:6 MANE Select	c.1242C>T	p.Asp414Asp	synonymous	Exon 1 of 1	ENSP00000358407.1

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

GnomAD2 exomes AF: 0.188 AC: 47325 AN: 251240 AF XY: 0.185

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 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

African (AFR) AF: 0.622 AC: 20812 AN: 33480

American (AMR) AF: 0.186 AC: 8317 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 3053 AN: 26136

East Asian (EAS) AF: 0.0672 AC: 2667 AN: 39700

South Asian (SAS) AF: 0.288 AC: 24863 AN: 86254

European-Finnish (FIN) AF: 0.178 AC: 9511 AN: 53362

Middle Eastern (MID) AF: 0.174 AC: 1001 AN: 5768

European-Non Finnish (NFE) AF: 0.125 AC: 139521 AN: 1112000

Other (OTH) AF: 0.173 AC: 10427 AN: 60396

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

African (AFR) AF: 0.601 AC: 24933 AN: 41452

American (AMR) AF: 0.183 AC: 2789 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 423 AN: 3470

East Asian (EAS) AF: 0.0955 AC: 494 AN: 5174

South Asian (SAS) AF: 0.293 AC: 1413 AN: 4820

European-Finnish (FIN) AF: 0.177 AC: 1878 AN: 10602

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8625 AN: 67996

Other (OTH) AF: 0.245 AC: 516 AN: 2110

Alfa AF: 0.173 Hom.: 11997

Bravo AF: 0.281

Asia WGS AF: 0.299 AC: 1038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.38
DANN	Benign	0.34
PhyloP100		-0.57
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

Other links and lift over

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