rs628977

Variant names:

• chr20-3669074-T-C
• rs628977
• NM_025220.5:c.2405-74A>G

Your query was ambiguous. Multiple possible variants found:

• chr20-3669074-T-C
• chr20-3669074-T-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.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. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 16 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.705 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.2405-74A>G		intron	N/A	NP_079496.1	Q9BZ11-1
	ADAM33	NM_001282447.3		c.2405-77A>G		intron	N/A	NP_001269376.1	A2A2L3
	ADAM33	NM_153202.4		c.2327-74A>G		intron	N/A	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.2405-74A>G		intron	N/A	ENSP00000348912.3	Q9BZ11-1
	ADAM33	ENST00000379861.8	TSL:1	c.2405-77A>G		intron	N/A	ENSP00000369190.4	A2A2L3
	ADAM33	ENST00000466620.5	TSL:1	n.1966-74A>G		intron	N/A

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

African (AFR) AF: 0.684 AC: 21485 AN: 31388

American (AMR) AF: 0.652 AC: 28874 AN: 44280

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 15472 AN: 25540

East Asian (EAS) AF: 0.604 AC: 23634 AN: 39148

South Asian (SAS) AF: 0.742 AC: 62366 AN: 84080

European-Finnish (FIN) AF: 0.617 AC: 32530 AN: 52702

Middle Eastern (MID) AF: 0.653 AC: 3528 AN: 5400

European-Non Finnish (NFE) AF: 0.630 AC: 652735 AN: 1035806

Other (OTH) AF: 0.645 AC: 37022 AN: 57416

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

African (AFR) AF: 0.680 AC: 28076 AN: 41292

American (AMR) AF: 0.672 AC: 10253 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2073 AN: 3462

East Asian (EAS) AF: 0.547 AC: 2800 AN: 5122

South Asian (SAS) AF: 0.725 AC: 3491 AN: 4812

European-Finnish (FIN) AF: 0.616 AC: 6464 AN: 10502

Middle Eastern (MID) AF: 0.658 AC: 192 AN: 292

European-Non Finnish (NFE) AF: 0.633 AC: 42876 AN: 67764

Other (OTH) AF: 0.651 AC: 1374 AN: 2112

Alfa AF: 0.642 Hom.: 6407

Bravo AF: 0.648

Asia WGS AF: 0.686 AC: 2384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.6
DANN	Benign	0.62
PhyloP100		0.37
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: rs628977;

hg19: chr20-3649721;

COSMIC: COSV62937563;