20-3674438-C-T

Variant names:

• chr20-3674438-C-T
• rs511898
• NM_025220.5:c.600+66G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025220.5(ADAM33):​c.600+66G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,600,968 control chromosomes in the GnomAD database, including 116,252 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 0.47 (18614 hom., cov: 33)
  • Exomes 𝑓: 0.36 (97638 hom.)
• Consequence: ADAM33 NM_025220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227
• Publications: 41 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025220.5. 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
	ADAM33	NM_025220.5	MANE Select	c.600+66G>A		intron	N/A	NP_079496.1
	ADAM33	NM_001282447.3		c.600+66G>A		intron	N/A	NP_001269376.1
	ADAM33	NM_153202.4		c.600+66G>A		intron	N/A	NP_694882.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM33	ENST00000356518.7	TSL:1 MANE Select	c.600+66G>A		intron	N/A	ENSP00000348912.3
	ADAM33	ENST00000379861.8	TSL:1	c.600+66G>A		intron	N/A	ENSP00000369190.4
	ADAM33	ENST00000350009.6	TSL:5	c.600+66G>A		intron	N/A	ENSP00000322550.5

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70627 AN: 151914 Hom.: 18569 Cov.: 33

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.446

GnomAD4 exome AF: 0.360 AC: 521660 AN: 1448936 Hom.: 97638 Cov.: 33 AF XY: 0.361 AC XY: 259536 AN XY: 719824

African (AFR) AF: 0.751 AC: 24646 AN: 32822

American (AMR) AF: 0.325 AC: 14161 AN: 43614

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 8706 AN: 25976

East Asian (EAS) AF: 0.332 AC: 13107 AN: 39486

South Asian (SAS) AF: 0.389 AC: 33236 AN: 85500

European-Finnish (FIN) AF: 0.449 AC: 23422 AN: 52188

Middle Eastern (MID) AF: 0.402 AC: 1833 AN: 4562

European-Non Finnish (NFE) AF: 0.344 AC: 380247 AN: 1105024

Other (OTH) AF: 0.373 AC: 22302 AN: 59764

GnomAD4 genome AF: 0.465 AC: 70729 AN: 152032 Hom.: 18614 Cov.: 33 AF XY: 0.466 AC XY: 34624 AN XY: 74286

African (AFR) AF: 0.735 AC: 30468 AN: 41448

American (AMR) AF: 0.362 AC: 5536 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1129 AN: 3470

East Asian (EAS) AF: 0.301 AC: 1552 AN: 5164

South Asian (SAS) AF: 0.381 AC: 1839 AN: 4828

European-Finnish (FIN) AF: 0.444 AC: 4683 AN: 10556

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24131 AN: 67964

Other (OTH) AF: 0.444 AC: 937 AN: 2108

Alfa AF: 0.373 Hom.: 14340

Bravo AF: 0.467

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	15
DANN	Benign	0.77
PhyloP100		0.23
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: rs511898; hg19: chr20-3655085;