Genetic Variant 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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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