16-89729077-C-T

Variant names:

• chr16-89729077-C-T
• rs7204478
• NM_001113525.2:c.1086-158C>T

Variant summary

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

The NM_001113525.2(ZNF276):​c.1086-158C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,938 control chromosomes in the GnomAD database, including 21,718 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 0.53 (21718 hom., cov: 32)
• Consequence: ZNF276 NM_001113525.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 26 publications found

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]

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]

FANCA Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen, G2P, Myriad Women’s Health
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113525.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF276	NM_001113525.2	MANE Select	c.1086-158C>T		intron	N/A	NP_001106997.1	Q8N554-1
	ZNF276	NM_152287.4		c.861-158C>T		intron	N/A	NP_689500.2
	ZNF276	NR_110122.2		n.1156-158C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF276	ENST00000443381.7	TSL:1 MANE Select	c.1086-158C>T		intron	N/A	ENSP00000415836.2	Q8N554-1
	ZNF276	ENST00000289816.9	TSL:1	c.861-158C>T		intron	N/A	ENSP00000289816.5	Q8N554-2
	ZNF276	ENST00000950694.1		c.1086-158C>T		intron	N/A	ENSP00000620753.1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80016 AN: 151820 Hom.: 21697 Cov.: 32

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.527 AC: 80080 AN: 151938 Hom.: 21718 Cov.: 32 AF XY: 0.537 AC XY: 39855 AN XY: 74254

African (AFR) AF: 0.601 AC: 24856 AN: 41384

American (AMR) AF: 0.584 AC: 8920 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1450 AN: 3472

East Asian (EAS) AF: 0.753 AC: 3882 AN: 5158

South Asian (SAS) AF: 0.687 AC: 3317 AN: 4828

European-Finnish (FIN) AF: 0.523 AC: 5521 AN: 10548

Middle Eastern (MID) AF: 0.503 AC: 147 AN: 292

European-Non Finnish (NFE) AF: 0.447 AC: 30408 AN: 67974

Other (OTH) AF: 0.512 AC: 1080 AN: 2108

Alfa AF: 0.472 Hom.: 34270

Bravo AF: 0.538

Asia WGS AF: 0.712 AC: 2477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.067
DANN	Benign	0.53
PhyloP100		-1.1
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: rs7204478; hg19: chr16-89795485;