dbSNP rs7095359: ADAM12:c.260+5882C>T (chr10-126273033-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001288973.2(ADAM12):c.260+5882C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 153,840 control chromosomes in the GnomAD database, including 41,265 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 ( 40776 hom., cov: 33)

Exomes 𝑓: 0.77 ( 489 hom. )

Consequence

ADAM12
NM_001288973.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.226

Publications

1 publications found

Variant links:

Genes affected

ADAM12 (HGNC:190): (ADAM metallopeptidase domain 12) This gene encodes a member of a family of proteins that are 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. Expression of this gene has been used as a maternal serum marker for pre-natal development. Alternative splicing results in multiple transcript variants encoding different isoforms. Shorter isoforms are secreted, while longer isoforms are membrane-bound form. [provided by RefSeq, Jan 2014]

ADAM12 links:

SAR1AP2 (HGNC:20770): (secretion associated Ras related GTPase 1A pseudogene 2)

SAR1AP2 links:

Genome browser will be placed here

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=-0.65).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM12	NM_001288973.2 link	c.260+5882C>T		intron_variant	Intron 3 of 22	ENST00000448723.2	NP_001275902.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADAM12	ENST00000448723.2 link	c.260+5882C>T	intron_variant	Intron 3 of 22	5	NM_001288973.2	ENSP00000391268.2	Q5JRP2
ADAM12	ENST00000368679.8 link	c.260+5882C>T	intron_variant	Intron 3 of 22	1		ENSP00000357668.4	O43184-1
ADAM12	ENST00000368676.8 link	c.260+5882C>T	intron_variant	Intron 3 of 18	1		ENSP00000357665.4	O43184-2
SAR1AP2	ENST00000392696.2 link	n.216G>A	non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

AF:

0.725

AC:

110342

AN:

152108

Hom.:

40773

Cov.:

show subpopulations

Gnomad AFR

AF:

0.583

Gnomad AMI

AF:

0.912

Gnomad AMR

AF:

0.678

Gnomad ASJ

AF:

0.722

Gnomad EAS

AF:

0.707

Gnomad SAS

AF:

0.747

Gnomad FIN

AF:

0.852

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.800

Gnomad OTH

AF:

0.726

GnomAD4 exome

AF:

0.768

AC:

1240

AN:

1614

Hom.:

489

Cov.:

AF XY:

0.768

AC XY:

728

AN XY:

948

show subpopulations

African (AFR)

AF:

0.604

AC:

AN:

American (AMR)

AF:

0.549

AC:

AN:

102

Ashkenazi Jewish (ASJ)

AF:

0.632

AC:

AN:

East Asian (EAS)

AF:

0.813

AC:

AN:

South Asian (SAS)

AF:

0.722

AC:

228

AN:

316

European-Finnish (FIN)

AF:

0.875

AC:

AN:

Middle Eastern (MID)

AF:

0.667

AC:

AN:

European-Non Finnish (NFE)

AF:

0.800

AC:

677

AN:

846

Other (OTH)

AF:

0.868

AC:

AN:

114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.725

AC:

110370

AN:

152226

Hom.:

40776

Cov.:

AF XY:

0.727

AC XY:

54117

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.582

AC:

24161

AN:

41510

American (AMR)

AF:

0.677

AC:

10358

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.722

AC:

2507

AN:

3470

East Asian (EAS)

AF:

0.707

AC:

3659

AN:

5172

South Asian (SAS)

AF:

0.748

AC:

3610

AN:

4826

European-Finnish (FIN)

AF:

0.852

AC:

9037

AN:

10608

Middle Eastern (MID)

AF:

0.765

AC:

225

AN:

294

European-Non Finnish (NFE)

AF:

0.800

AC:

54448

AN:

68022

Other (OTH)

AF:

0.725

AC:

1533

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1501

3003

4504

6006

7507

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

838

1676

2514

3352

4190

<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:

0.764

Hom.:

57173

Bravo

AF:

0.705

Asia WGS

AF:

0.726

AC:

2526

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

2.1

(source)

DANN

Benign

0.49

PhyloP100

-0.23

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over