rs17111967

chr14-20456166-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001641.4(APEX1):c.246+65C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00715 in 1,565,950 control chromosomes in the GnomAD database, including 49 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 0.0043 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0075 (47 hom.)
• Consequence: APEX1 NM_001641.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.558

Genes affected

APEX1 (HGNC:587): (apurinic/apyrimidinic endodeoxyribonuclease 1) The APEX gene encodes the major AP endonuclease in human cells. It encodes the APEX endonuclease, a DNA repair enzyme with apurinic/apyrimidinic (AP) activity. Such AP activity sites occur frequently in DNA molecules by spontaneous hydrolysis, by DNA damaging agents or by DNA glycosylases that remove specific abnormal bases. The AP sites are the most frequent pre-mutagenic lesions that can prevent normal DNA replication. Splice variants have been found for this gene; all encode the same protein. Disruptions in the biological functions related to APEX are associated with many various malignancies and neurodegenerative diseases.[provided by RefSeq, Dec 2019]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APEX1	NM_001641.4	c.246+65C>T		intron_variant		ENST00000216714.8
APEX1	NM_001244249.2	c.246+65C>T		intron_variant
APEX1	NM_080648.3	c.246+65C>T		intron_variant
APEX1	NM_080649.3	c.246+65C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APEX1	ENST00000216714.8	c.246+65C>T		intron_variant		1	NM_001641.4	P1

Frequencies

GnomAD3 genomes AF: 0.00433 AC: 659 AN: 152182 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00123

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00772

Gnomad OTH AF: 0.00575

GnomAD4 exome AF: 0.00745 AC: 10533 AN: 1413650 Hom.: 47 AF XY: 0.00725 AC XY: 5119 AN XY: 705602

Gnomad4 AFR exome AF: 0.00164

Gnomad4 AMR exome AF: 0.00282

Gnomad4 ASJ exome AF: 0.00128

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.00318

Gnomad4 FIN exome AF: 0.00196

Gnomad4 NFE exome AF: 0.00900

Gnomad4 OTH exome AF: 0.00531

GnomAD4 genome AF: 0.00431 AC: 656 AN: 152300 Hom.: 2 Cov.: 32 AF XY: 0.00397 AC XY: 296 AN XY: 74470

Gnomad4 AFR AF: 0.00115

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.00123

Gnomad4 NFE AF: 0.00770

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00508 Hom.: 0

Bravo AF: 0.00430

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	3.0
Dann	Benign	0.75

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: rs17111967; hg19: chr14-20924325;