chr10-126241146-G-T

Position:

• chr10-126241146-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+37769C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 152,076 control chromosomes in the GnomAD database, including 24,728 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 0.56 (24728 hom., cov: 33)
• Consequence: ADAM12 NM_001288973.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM12	NM_001288973.2	c.260+37769C>A		intron_variant		ENST00000448723.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM12	ENST00000448723.2	c.260+37769C>A		intron_variant		5	NM_001288973.2	A2
ADAM12	ENST00000368676.8	c.260+37769C>A		intron_variant		1		A2
ADAM12	ENST00000368679.8	c.260+37769C>A		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85442 AN: 151958 Hom.: 24691 Cov.: 33

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.535

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.563 AC: 85545 AN: 152076 Hom.: 24728 Cov.: 33 AF XY: 0.563 AC XY: 41831 AN XY: 74314

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.636

Gnomad4 SAS AF: 0.661

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.537

Alfa AF: 0.498 Hom.: 31805

Bravo AF: 0.575

Asia WGS AF: 0.658 AC: 2290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.22

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: rs4962528; hg19: chr10-127929715;