rs1892284

Positions:

• chr14-70453021-A-G
• chr14-70453021-A-T

Variant summary

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

The NM_003813.4(ADAM21):​c.-152+758A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.915 in 152,116 control chromosomes in the GnomAD database, including 64,144 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 0.91 (64144 hom., cov: 30)
• Consequence: ADAM21 NM_003813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

Genes affected

ADAM21 (HGNC:200): (ADAM metallopeptidase domain 21) 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 expression is testis-specific. [provided by RefSeq, May 2011]

ENSG00000257759 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM21	NM_003813.4	c.-152+758A>G		intron_variant		ENST00000603540.2	NP_003804.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM21	ENST00000603540.2	c.-152+758A>G		intron_variant		3	NM_003813.4	ENSP00000474385.1
ADAM21	ENST00000679631.1	c.-151-4328A>G		intron_variant				ENSP00000506213.1
ENSG00000257759	ENST00000556646.1	n.286+386T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.915 AC: 139045 AN: 151998 Hom.: 64096 Cov.: 30

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.942

Gnomad ASJ AF: 0.948

Gnomad EAS AF: 0.921

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.965

Gnomad OTH AF: 0.926

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

GnomAD4 genome AF: 0.915 AC: 139149 AN: 152116 Hom.: 64144 Cov.: 30 AF XY: 0.914 AC XY: 67993 AN XY: 74350

Gnomad4 AFR AF: 0.795

Gnomad4 AMR AF: 0.943

Gnomad4 ASJ AF: 0.948

Gnomad4 EAS AF: 0.921

Gnomad4 SAS AF: 0.917

Gnomad4 FIN AF: 0.996

Gnomad4 NFE AF: 0.965

Gnomad4 OTH AF: 0.926

Alfa AF: 0.945 Hom.: 14630

Bravo AF: 0.906

Asia WGS AF: 0.915 AC: 3184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.0
DANN	Benign	0.67

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: rs1892284; hg19: chr14-70919738;