rs4785714

Positions:

• chr16-89731996-C-A
• chr16-89731996-C-T

Variant summary

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

The NM_001113525.2(ZNF276):​c.1170-1306C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,192 control chromosomes in the GnomAD database, including 9,594 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 0.33 (9590 hom., cov: 33)
  • Exomes 𝑓: 0.50 (4 hom.)
• Consequence: ZNF276 NM_001113525.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.942

Genes affected

ZNF276 (HGNC:23330): (zinc finger protein 276) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in kinetochore. [provided by Alliance of Genome Resources, Apr 2022]

ZNF276 (HGNC:):

FANCA (HGNC:3582): (FA complementation group A) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group A. Alternative splicing results in multiple transcript variants encoding different isoforms. Mutations in this gene are the most common cause of Fanconi anemia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF276	NM_001113525.2	c.1170-1306C>A		intron_variant		ENST00000443381.7	NP_001106997.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF276	ENST00000443381.7	c.1170-1306C>A		intron_variant		1	NM_001113525.2	ENSP00000415836.2

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50568 AN: 152046 Hom.: 9590 Cov.: 33

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.0137

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.368

GnomAD4 exome AF: 0.500 AC: 14 AN: 28 Hom.: 4 Cov.: 0 AF XY: 0.389 AC XY: 7 AN XY: 18

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.455

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.332 AC: 50588 AN: 152164 Hom.: 9590 Cov.: 33 AF XY: 0.326 AC XY: 24224 AN XY: 74410

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.0137

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.429

Gnomad4 OTH AF: 0.364

Alfa AF: 0.300 Hom.: 1516

Bravo AF: 0.321

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.73

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: rs4785714; hg19: chr16-89798404;