10-126241146-G-T

Variant names:

• chr10-126241146-G-T
• rs4962528
• NM_001288973.2:c.260+37769C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288973.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM12	NM_001288973.2	MANE Select	c.260+37769C>A		intron	N/A	NP_001275902.1
	ADAM12	NM_003474.6		c.260+37769C>A		intron	N/A	NP_003465.3
	ADAM12	NM_021641.5		c.260+37769C>A		intron	N/A	NP_067673.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM12	ENST00000448723.2	TSL:5 MANE Select	c.260+37769C>A		intron	N/A	ENSP00000391268.2
	ADAM12	ENST00000368679.8	TSL:1	c.260+37769C>A		intron	N/A	ENSP00000357668.4
	ADAM12	ENST00000368676.8	TSL:1	c.260+37769C>A		intron	N/A	ENSP00000357665.4

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

African (AFR) AF: 0.690 AC: 28635 AN: 41502

American (AMR) AF: 0.583 AC: 8911 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1967 AN: 3472

East Asian (EAS) AF: 0.636 AC: 3279 AN: 5154

South Asian (SAS) AF: 0.661 AC: 3189 AN: 4828

European-Finnish (FIN) AF: 0.480 AC: 5059 AN: 10540

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32861 AN: 67976

Other (OTH) AF: 0.537 AC: 1135 AN: 2112

Alfa AF: 0.516 Hom.: 56131

Bravo AF: 0.575

Asia WGS AF: 0.658 AC: 2290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.22
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4962528; hg19: chr10-127929715;