12-107515788-A-G

Position:

• chr12-107515788-A-G

Variant summary

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

The NM_001018072.2(ABTB3):​c.1136-4699A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,926 control chromosomes in the GnomAD database, including 12,050 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 0.39 (12050 hom., cov: 31)
• Consequence: ABTB3 NM_001018072.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508

Genes affected

ABTB3 (HGNC:23844): (ankyrin repeat and BTB domain containing 3) Predicted to enable protein heterodimerization activity. Predicted to be involved in SMAD protein signal transduction. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABTB3	NM_001018072.2	c.1136-4699A>G		intron_variant		ENST00000280758.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABTB3	ENST00000280758.10	c.1136-4699A>G		intron_variant		5	NM_001018072.2

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58874 AN: 151808 Hom.: 12015 Cov.: 31

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.388 AC: 58973 AN: 151926 Hom.: 12050 Cov.: 31 AF XY: 0.381 AC XY: 28320 AN XY: 74258

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.390

Alfa AF: 0.277 Hom.: 1002

Bravo AF: 0.416

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.73
DANN	Benign	0.72

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: rs11835314; hg19: chr12-107909565;