12-19425173-T-C

Variant names:

• chr12-19425173-T-C
• rs2961365
• ENST00000541908.5:c.-17+21049T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000541908.5(AEBP2):​c.-17+21049T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 152,142 control chromosomes in the GnomAD database, including 55,029 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 0.85 (55029 hom., cov: 32)
• Consequence: AEBP2 ENST00000541908.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.81
• Publications: 5 publications found

Genes affected

AEBP2 (HGNC:24051): (AE binding protein 2) Predicted to enable transcription coregulator activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within regulation of transcription, DNA-templated. Located in nucleoplasm. Part of ESC/E(Z) complex. [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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AEBP2	XM_017018806.2	c.-17+21049T>C		intron_variant	Intron 1 of 8		XP_016874295.1
AEBP2	XM_047428299.1	c.-17+20957T>C		intron_variant	Intron 1 of 8		XP_047284255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AEBP2	ENST00000541908.5	c.-17+21049T>C		intron_variant	Intron 1 of 7	3		ENSP00000437983.1
AEBP2	ENST00000538425.5	c.-17+20957T>C		intron_variant	Intron 1 of 3	4		ENSP00000444255.1

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128960 AN: 152024 Hom.: 54993 Cov.: 32

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.865

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.827

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

GnomAD4 genome AF: 0.848 AC: 129049 AN: 152142 Hom.: 55029 Cov.: 32 AF XY: 0.848 AC XY: 63089 AN XY: 74358

African (AFR) AF: 0.925 AC: 38402 AN: 41534

American (AMR) AF: 0.793 AC: 12103 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 2663 AN: 3470

East Asian (EAS) AF: 0.829 AC: 4273 AN: 5152

South Asian (SAS) AF: 0.735 AC: 3532 AN: 4808

European-Finnish (FIN) AF: 0.865 AC: 9159 AN: 10586

Middle Eastern (MID) AF: 0.764 AC: 223 AN: 292

European-Non Finnish (NFE) AF: 0.826 AC: 56149 AN: 68010

Other (OTH) AF: 0.828 AC: 1749 AN: 2112

Alfa AF: 0.826 Hom.: 158008

Bravo AF: 0.846

Asia WGS AF: 0.799 AC: 2779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.045
DANN	Benign	0.37
PhyloP100		-3.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2961365; hg19: chr12-19578107;