chr12-107454875-T-C

Variant names:

• chr12-107454875-T-C
• rs933880
• NM_001018072.2:c.1136-65612T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018072.2. 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
	ABTB3	NM_001018072.2	MANE Select	c.1136-65612T>C		intron	N/A	NP_001018082.1
	ABTB3	NM_001347943.2		c.1136-65612T>C		intron	N/A	NP_001334872.1
	ABTB3	NM_001347944.1		c.38-65612T>C		intron	N/A	NP_001334873.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABTB3	ENST00000280758.10	TSL:5 MANE Select	c.1136-65612T>C		intron	N/A	ENSP00000280758.5
	ABTB3	ENST00000490090.6	TSL:2	c.1136-65612T>C		intron	N/A	ENSP00000447319.1
	ABTB3	ENST00000420571.6	TSL:5	c.1136-65612T>C		intron	N/A	ENSP00000413889.2

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

African (AFR) AF: 0.658 AC: 27279 AN: 41464

American (AMR) AF: 0.518 AC: 7925 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 951 AN: 3470

East Asian (EAS) AF: 0.775 AC: 4000 AN: 5158

South Asian (SAS) AF: 0.398 AC: 1917 AN: 4820

European-Finnish (FIN) AF: 0.326 AC: 3446 AN: 10576

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21439 AN: 67972

Other (OTH) AF: 0.427 AC: 903 AN: 2116

Alfa AF: 0.365 Hom.: 20956

Bravo AF: 0.474

Asia WGS AF: 0.594 AC: 2066 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.7
DANN	Benign	0.77
PhyloP100		-0.21
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: rs933880; hg19: chr12-107848652;