dbSNP rs11101672: ADAM8:c.2064-132C>G (chr10-133268250-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001109.5(ADAM8):c.2064-132C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 840,092 control chromosomes in the GnomAD database, including 288,767 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 0.73 ( 43245 hom., cov: 34)

Exomes 𝑓: 0.84 ( 245522 hom. )

Consequence

ADAM8
NM_001109.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.542

Publications

6 publications found

Variant links:

Genes affected

ADAM8 (HGNC:215): (ADAM metallopeptidase domain 8) 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. The protein encoded by this gene may be involved in cell adhesion during neurodegeneration, and it is thought to be a target for allergic respiratory diseases, including asthma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2009]

ADAM8 links:

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ACMG classification

Classification was made for transcript

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 = 0.905 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001109.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADAM8	NM_001109.5	MANE Select	c.2064-132C>G	intron	N/A	NP_001100.3	P78325-1
ADAM8	NM_001164489.2		c.1949-184C>G	intron	N/A	NP_001157961.1	P78325-3
ADAM8	NM_001164490.2		c.1869-132C>G	intron	N/A	NP_001157962.1	P78325-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADAM8	ENST00000445355.8	TSL:1 MANE Select	c.2064-132C>G	intron	N/A	ENSP00000453302.1	P78325-1
ADAM8	ENST00000415217.7	TSL:1	c.1949-184C>G	intron	N/A	ENSP00000453855.1	P78325-3
ADAM8	ENST00000897047.1		c.2058-132C>G	intron	N/A	ENSP00000567106.1

Frequencies

GnomAD3 genomes

AF:

0.732

AC:

111391

AN:

152094

Hom.:

43227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.451

Gnomad AMI

AF:

0.792

Gnomad AMR

AF:

0.744

Gnomad ASJ

AF:

0.844

Gnomad EAS

AF:

0.926

Gnomad SAS

AF:

0.843

Gnomad FIN

AF:

0.888

Gnomad MID

AF:

0.753

Gnomad NFE

AF:

0.847

Gnomad OTH

AF:

0.751

GnomAD4 exome

AF:

0.842

AC:

579196

AN:

687880

Hom.:

245522

AF XY:

0.842

AC XY:

280274

AN XY:

332670

show subpopulations

African (AFR)

AF:

0.444

AC:

6646

AN:

14964

American (AMR)

AF:

0.744

AC:

6502

AN:

8740

Ashkenazi Jewish (ASJ)

AF:

0.854

AC:

10205

AN:

11950

East Asian (EAS)

AF:

0.907

AC:

22402

AN:

24708

South Asian (SAS)

AF:

0.841

AC:

9913

AN:

11792

European-Finnish (FIN)

AF:

0.882

AC:

30569

AN:

34664

Middle Eastern (MID)

AF:

0.799

AC:

1833

AN:

2294

European-Non Finnish (NFE)

AF:

0.850

AC:

466342

AN:

548344

Other (OTH)

AF:

0.815

AC:

24784

AN:

30424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

4619

9238

13856

18475

23094

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10494

20988

31482

41976

52470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.732

AC:

111444

AN:

152212

Hom.:

43245

Cov.:

AF XY:

0.739

AC XY:

54980

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.451

AC:

18726

AN:

41526

American (AMR)

AF:

0.744

AC:

11373

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.844

AC:

2930

AN:

3472

East Asian (EAS)

AF:

0.927

AC:

4791

AN:

5168

South Asian (SAS)

AF:

0.843

AC:

4071

AN:

4828

European-Finnish (FIN)

AF:

0.888

AC:

9422

AN:

10616

Middle Eastern (MID)

AF:

0.759

AC:

223

AN:

294

European-Non Finnish (NFE)

AF:

0.847

AC:

57597

AN:

67994

Other (OTH)

AF:

0.754

AC:

1592

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1326

2652

3977

5303

6629

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

828

1656

2484

3312

4140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.778

Hom.:

5957

Bravo

AF:

0.709

Asia WGS

AF:

0.853

AC:

2967

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

0.26

(source)

DANN

Benign

0.40

PhyloP100

-0.54

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over