12-107454875-T-C

Variant summary

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

The NM_001018072.2(ABTB3):c.1136-65612T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,070 control chromosomes in the GnomAD database, including 17,434 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 0.45 (17434 hom., cov: 33)
• Consequence: ABTB3 NM_001018072.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABTB3	NM_001018072.2	c.1136-65612T>C		intron_variant		ENST00000280758.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABTB3	ENST00000280758.10	c.1136-65612T>C		intron_variant		5	NM_001018072.2

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68079 AN: 151952 Hom.: 17382 Cov.: 33

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.448 AC: 68193 AN: 152070 Hom.: 17434 Cov.: 33 AF XY: 0.451 AC XY: 33541 AN XY: 74326

Gnomad4 AFR AF: 0.658

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.427

Alfa AF: 0.348 Hom.: 13671

Bravo AF: 0.474

Asia WGS AF: 0.594 AC: 2066 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	1.7
Dann	Benign	0.77

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: rs933880; hg19: chr12-107848652;