rs12590471

chr14-70534383-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003814.5(ADAM20):c.-177+414C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 151,698 control chromosomes in the GnomAD database, including 6,980 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 0.26 (6980 hom., cov: 31)
• Consequence: ADAM20 NM_003814.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

Genes affected

ADAM20 (HGNC:199): (ADAM metallopeptidase domain 20) 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. The expression of this gene is testis-specific. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM20	NM_003814.5	c.-177+414C>T		intron_variant		ENST00000256389.5
LOC105370556	XR_007064239.1	n.69-3002G>A		intron_variant, non_coding_transcript_variant
ADAM20	XM_005268151.4	c.-26-9450C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM20	ENST00000256389.5	c.-177+414C>T		intron_variant		1	NM_003814.5	P2
	ENST00000556646.1	n.183+12899C>T		intron_variant, non_coding_transcript_variant		4
ADAM20	ENST00000652041.1	c.-27+414C>T		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39416 AN: 151580 Hom.: 6954 Cov.: 31

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.0985

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.258

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.260 AC: 39496 AN: 151698 Hom.: 6980 Cov.: 31 AF XY: 0.260 AC XY: 19235 AN XY: 74086

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.0985

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.265

Alfa AF: 0.197 Hom.: 1940

Bravo AF: 0.279

Asia WGS AF: 0.444 AC: 1543 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.0
Dann	Benign	0.68

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: rs12590471; hg19: chr14-71001100;