20-3669074-T-C

Position:

• chr20-3669074-T-C

Variant summary

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

The NM_025220.5(ADAM33):​c.2405-74A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 1,527,280 control chromosomes in the GnomAD database, including 313,565 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 0.65 (31992 hom., cov: 32)
  • Exomes 𝑓: 0.64 (281573 hom.)
• Consequence: ADAM33 NM_025220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372

Genes affected

ADAM33 (HGNC:15478): (ADAM metallopeptidase domain 33) 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 protein is a type I transmembrane protein implicated in asthma and bronchial hyperresponsiveness. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2013]

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 (SAS) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM33	NM_025220.5	c.2405-74A>G		intron_variant		ENST00000356518.7	NP_079496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM33	ENST00000356518.7	c.2405-74A>G		intron_variant		1	NM_025220.5	ENSP00000348912	P4

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98115 AN: 151404 Hom.: 31958 Cov.: 32

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.648

GnomAD4 exome AF: 0.638 AC: 877646 AN: 1375760 Hom.: 281573 Cov.: 23 AF XY: 0.642 AC XY: 442371 AN XY: 689352

Gnomad4 AFR exome AF: 0.684

Gnomad4 AMR exome AF: 0.652

Gnomad4 ASJ exome AF: 0.606

Gnomad4 EAS exome AF: 0.604

Gnomad4 SAS exome AF: 0.742

Gnomad4 FIN exome AF: 0.617

Gnomad4 NFE exome AF: 0.630

Gnomad4 OTH exome AF: 0.645

GnomAD4 genome AF: 0.648 AC: 98198 AN: 151520 Hom.: 31992 Cov.: 32 AF XY: 0.648 AC XY: 47960 AN XY: 74002

Gnomad4 AFR AF: 0.680

Gnomad4 AMR AF: 0.672

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.725

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.651

Alfa AF: 0.641 Hom.: 5434

Bravo AF: 0.648

Asia WGS AF: 0.686 AC: 2384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.6
DANN	Benign	0.62

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: rs628977; hg19: chr20-3649721; COSMIC: COSV62937563;