14-70453021-A-G

Variant names:

• chr14-70453021-A-G
• rs1892284
• NM_003813.4:c.-152+758A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003813.4. 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
	ADAM21	NM_003813.4	MANE Select	c.-152+758A>G		intron	N/A	NP_003804.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM21	ENST00000603540.2	TSL:3 MANE Select	c.-152+758A>G		intron	N/A	ENSP00000474385.1
	ADAM21	ENST00000679631.1		c.-151-4328A>G		intron	N/A	ENSP00000506213.1
	ENSG00000257759	ENST00000556646.1	TSL:4	n.286+386T>C		intron	N/A

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

African (AFR) AF: 0.795 AC: 32923 AN: 41430

American (AMR) AF: 0.943 AC: 14415 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.948 AC: 3291 AN: 3472

East Asian (EAS) AF: 0.921 AC: 4762 AN: 5170

South Asian (SAS) AF: 0.917 AC: 4413 AN: 4810

European-Finnish (FIN) AF: 0.996 AC: 10562 AN: 10604

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.965 AC: 65652 AN: 68024

Other (OTH) AF: 0.926 AC: 1951 AN: 2106

Alfa AF: 0.942 Hom.: 14882

Bravo AF: 0.906

Asia WGS AF: 0.915 AC: 3184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.0
DANN	Benign	0.67
PhyloP100		-1.1
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: rs1892284; hg19: chr14-70919738;