12-107457403-C-T

Position:

• chr12-107457403-C-T

Variant summary

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

The NM_001018072.2(ABTB3):​c.1136-63084C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,202 control chromosomes in the GnomAD database, including 1,540 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 0.14 (1540 hom., cov: 33)
• Consequence: ABTB3 NM_001018072.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.55

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=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABTB3	NM_001018072.2	c.1136-63084C>T		intron_variant		ENST00000280758.10	NP_001018082.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABTB3	ENST00000280758.10	c.1136-63084C>T		intron_variant		5	NM_001018072.2	ENSP00000280758

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20714 AN: 152084 Hom.: 1538 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0944

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.136 AC: 20733 AN: 152202 Hom.: 1540 Cov.: 33 AF XY: 0.134 AC XY: 9969 AN XY: 74416

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.0944

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.136

Alfa AF: 0.146 Hom.: 2237

Bravo AF: 0.139

Asia WGS AF: 0.220 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.8
DANN	Benign	0.83

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: rs10861741; hg19: chr12-107851180;