chr10-126093840-C-T

Position:

• chr10-126093840-C-T

Variant summary

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

The NM_001288973.2(ADAM12):​c.1145+145G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 1,293,756 control chromosomes in the GnomAD database, including 156,911 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 0.49 (18710 hom., cov: 33)
  • Exomes 𝑓: 0.49 (138201 hom.)
• Consequence: ADAM12 NM_001288973.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.568

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM12	NM_001288973.2	c.1145+145G>A		intron_variant		ENST00000448723.2	NP_001275902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM12	ENST00000448723.2	c.1145+145G>A		intron_variant		5	NM_001288973.2	ENSP00000391268.2
ADAM12	ENST00000368679.8	c.1154+145G>A		intron_variant		1		ENSP00000357668.4
ADAM12	ENST00000368676.8	c.1154+145G>A		intron_variant		1		ENSP00000357665.4
ADAM12	ENST00000485388.2	n.124-2847G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75102 AN: 151940 Hom.: 18686 Cov.: 33

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.526

GnomAD4 exome AF: 0.489 AC: 558689 AN: 1141698 Hom.: 138201 AF XY: 0.490 AC XY: 279418 AN XY: 570560

Gnomad4 AFR exome AF: 0.527

Gnomad4 AMR exome AF: 0.430

Gnomad4 ASJ exome AF: 0.586

Gnomad4 EAS exome AF: 0.422

Gnomad4 SAS exome AF: 0.468

Gnomad4 FIN exome AF: 0.513

Gnomad4 NFE exome AF: 0.491

Gnomad4 OTH exome AF: 0.488

GnomAD4 genome AF: 0.494 AC: 75166 AN: 152058 Hom.: 18710 Cov.: 33 AF XY: 0.496 AC XY: 36878 AN XY: 74350

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.534

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.525

Alfa AF: 0.488 Hom.: 23678

Bravo AF: 0.491

Asia WGS AF: 0.452 AC: 1571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.2
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1871054; hg19: chr10-127782409; COSMIC: COSV64103782;