chr20-3672502-C-A

Variant names:

• chr20-3672502-C-A
• rs3918395
• NM_025220.5:c.1401+35G>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.1401+35G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,603,666 control chromosomes in the GnomAD database, including 13,902 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 0.13 (1303 hom., cov: 34)
  • Exomes 𝑓: 0.13 (12599 hom.)
• Consequence: ADAM33 NM_025220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560
• Publications: 21 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=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.149 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.1401+35G>T		intron	N/A	NP_079496.1
	ADAM33	NM_001282447.3		c.1401+35G>T		intron	N/A	NP_001269376.1
	ADAM33	NM_153202.4		c.1401+35G>T		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.1401+35G>T		intron	N/A	ENSP00000348912.3
	ADAM33	ENST00000379861.8	TSL:1	c.1401+35G>T		intron	N/A	ENSP00000369190.4
	ADAM33	ENST00000466620.5	TSL:1	n.1040+35G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19899 AN: 152140 Hom.: 1302 Cov.: 34

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0957

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.140

GnomAD2 exomes AF: 0.129 AC: 30868 AN: 239596 AF XY: 0.134

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.0659

Gnomad ASJ exome AF: 0.131

Gnomad EAS exome AF: 0.0848

Gnomad FIN exome AF: 0.173

Gnomad NFE exome AF: 0.136

Gnomad OTH exome AF: 0.142

GnomAD4 exome AF: 0.129 AC: 187561 AN: 1451408 Hom.: 12599 Cov.: 36 AF XY: 0.132 AC XY: 94723 AN XY: 720214

African (AFR) AF: 0.121 AC: 4023 AN: 33220

American (AMR) AF: 0.0690 AC: 3036 AN: 43994

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 3363 AN: 25878

East Asian (EAS) AF: 0.109 AC: 4305 AN: 39462

South Asian (SAS) AF: 0.173 AC: 14836 AN: 85850

European-Finnish (FIN) AF: 0.180 AC: 9473 AN: 52710

Middle Eastern (MID) AF: 0.199 AC: 1138 AN: 5722

European-Non Finnish (NFE) AF: 0.126 AC: 139408 AN: 1104786

Other (OTH) AF: 0.133 AC: 7979 AN: 59786

GnomAD4 genome AF: 0.131 AC: 19898 AN: 152258 Hom.: 1303 Cov.: 34 AF XY: 0.132 AC XY: 9846 AN XY: 74442

African (AFR) AF: 0.124 AC: 5143 AN: 41566

American (AMR) AF: 0.108 AC: 1649 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 426 AN: 3472

East Asian (EAS) AF: 0.0959 AC: 495 AN: 5162

South Asian (SAS) AF: 0.159 AC: 766 AN: 4828

European-Finnish (FIN) AF: 0.173 AC: 1834 AN: 10620

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9123 AN: 67992

Other (OTH) AF: 0.138 AC: 292 AN: 2110

Alfa AF: 0.129 Hom.: 2259

Bravo AF: 0.121

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.0
DANN	Benign	0.80
PhyloP100		0.056
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3918395; hg19: chr20-3653149; COSMIC: COSV107436257; COSMIC: COSV107436257;