rs7095359

chr10-126273033-G-Achr10-126273033-G-Cchr10-126273033-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226

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]

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

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ADAM12	NM_001288973.2	c.260+5882C>T		intron_variant		ENST00000448723.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM12	ENST00000448723.2	c.260+5882C>T		intron_variant		5	NM_001288973.2	A2
ADAM12	ENST00000368676.8	c.260+5882C>T		intron_variant		1		A2
ADAM12	ENST00000368679.8	c.260+5882C>T		intron_variant		1		P2
SAR1AP2	ENST00000392696.2	n.216G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110342 AN: 152108 Hom.: 40773 Cov.: 33

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.: 0 AF XY: 0.768 AC XY: 728 AN XY: 948

Gnomad4 AFR exome AF: 0.604

Gnomad4 AMR exome AF: 0.549

Gnomad4 ASJ exome AF: 0.632

Gnomad4 EAS exome AF: 0.813

Gnomad4 SAS exome AF: 0.722

Gnomad4 FIN exome AF: 0.875

Gnomad4 NFE exome AF: 0.800

Gnomad4 OTH exome AF: 0.868

GnomAD4 genome AF: 0.725 AC: 110370 AN: 152226 Hom.: 40776 Cov.: 33 AF XY: 0.727 AC XY: 54117 AN XY: 74436

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.722

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.748

Gnomad4 FIN AF: 0.852

Gnomad4 NFE AF: 0.800

Gnomad4 OTH AF: 0.725

Alfa AF: 0.774 Hom.: 44386

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
Dann	Benign	0.49

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

LitVar

Other links and lift over

dbSNP: rs7095359; hg19: chr10-127961602;