rs3918400

Variant names:

• chr20-3668816-G-A
• rs3918400
• NM_025220.5:c.*147C>T

Variant summary

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

The NM_025220.5(ADAM33):​c.*147C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0441 in 972,232 control chromosomes in the GnomAD database, including 1,401 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 0.060 (353 hom., cov: 32)
  • Exomes 𝑓: 0.041 (1048 hom.)
• Consequence: ADAM33 NM_025220.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 14 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM33	NM_025220.5	MANE Select	c.*147C>T		3_prime_UTR	Exon 22 of 22	NP_079496.1	Q9BZ11-1
	ADAM33	NM_001282447.3		c.*147C>T		3_prime_UTR	Exon 22 of 22	NP_001269376.1	A2A2L3
	ADAM33	NM_153202.4		c.*147C>T		3_prime_UTR	Exon 21 of 21	NP_694882.1	Q9BZ11-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM33	ENST00000356518.7	TSL:1 MANE Select	c.*147C>T		3_prime_UTR	Exon 22 of 22	ENSP00000348912.3	Q9BZ11-1
	ADAM33	ENST00000379861.8	TSL:1	c.*147C>T		3_prime_UTR	Exon 22 of 22	ENSP00000369190.4	A2A2L3
	ADAM33	ENST00000466620.5	TSL:1	n.2150C>T		non_coding_transcript_exon	Exon 11 of 11

Frequencies

GnomAD3 genomes AF: 0.0605 AC: 9195 AN: 152078 Hom.: 354 Cov.: 32

Gnomad AFR AF: 0.0901

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0940

Gnomad ASJ AF: 0.0351

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.0614

Gnomad FIN AF: 0.0289

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0355

Gnomad OTH AF: 0.0584

GnomAD4 exome AF: 0.0411 AC: 33666 AN: 820036 Hom.: 1048 Cov.: 11 AF XY: 0.0412 AC XY: 17711 AN XY: 429756

African (AFR) AF: 0.0838 AC: 1764 AN: 21058

American (AMR) AF: 0.0812 AC: 3396 AN: 41824

Ashkenazi Jewish (ASJ) AF: 0.0307 AC: 636 AN: 20710

East Asian (EAS) AF: 0.132 AC: 4738 AN: 35832

South Asian (SAS) AF: 0.0503 AC: 3478 AN: 69168

European-Finnish (FIN) AF: 0.0288 AC: 1143 AN: 39636

Middle Eastern (MID) AF: 0.0378 AC: 110 AN: 2912

European-Non Finnish (NFE) AF: 0.0302 AC: 16594 AN: 549818

Other (OTH) AF: 0.0462 AC: 1807 AN: 39078

GnomAD4 genome AF: 0.0604 AC: 9196 AN: 152196 Hom.: 353 Cov.: 32 AF XY: 0.0618 AC XY: 4601 AN XY: 74404

African (AFR) AF: 0.0899 AC: 3732 AN: 41508

American (AMR) AF: 0.0938 AC: 1434 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0351 AC: 122 AN: 3472

East Asian (EAS) AF: 0.141 AC: 733 AN: 5182

South Asian (SAS) AF: 0.0616 AC: 297 AN: 4820

European-Finnish (FIN) AF: 0.0289 AC: 307 AN: 10612

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0355 AC: 2411 AN: 67998

Other (OTH) AF: 0.0582 AC: 123 AN: 2112

Alfa AF: 0.0486 Hom.: 50

Bravo AF: 0.0662

Asia WGS AF: 0.0960 AC: 331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.45
DANN	Benign	0.68
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3918400;

hg19: chr20-3649463;