rs1542313

chr14-64533320-A-Cchr14-64533320-A-Gchr14-64533320-A-T

Variant summary

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

The ENST00000358738.3(ZBTB1):c.*1423A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 152,108 control chromosomes in the GnomAD database, including 20,076 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 0.51 (20012 hom., cov: 31)
  • Exomes 𝑓: 0.64 (64 hom.)
• Consequence: ZBTB1 ENST00000358738.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.368

Genes affected

ZBTB1 (HGNC:20259): (zinc finger and BTB domain containing 1) Enables K63-linked polyubiquitin modification-dependent protein binding activity; protein heterodimerization activity; and protein homodimerization activity. Involved in several processes, including cellular response to UV; nucleobase-containing compound biosynthetic process; and protein homooligomerization. Located in centrosome; nuclear body; and nuclear membrane. [provided by Alliance of Genome Resources, Apr 2022]

HSPA2-AS1 (HGNC:55433): (HSPA2 and ZBTB1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA2-AS1	NR_110550.1	n.53-751T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB1	ENST00000358738.3	c.*1423A>C		3_prime_UTR_variant	3/3	1
HSPA2-AS1	ENST00000554918.1	n.53-751T>G		intron_variant, non_coding_transcript_variant		3
HSPA2-AS1	ENST00000648003.1	n.475-751T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77275 AN: 151692 Hom.: 19997 Cov.: 31

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.429

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.485

GnomAD4 exome AF: 0.644 AC: 192 AN: 298 Hom.: 64 Cov.: 0 AF XY: 0.642 AC XY: 122 AN XY: 190

Gnomad4 FIN exome AF: 0.646

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.509 AC: 77330 AN: 151810 Hom.: 20012 Cov.: 31 AF XY: 0.518 AC XY: 38447 AN XY: 74214

Gnomad4 AFR AF: 0.493

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.655

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.488

Alfa AF: 0.481 Hom.: 11044

Bravo AF: 0.507

Asia WGS AF: 0.570 AC: 1970 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.60
Dann	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1542313; hg19: chr14-65000038;