16-89739935-C-A

Position:

• chr16-89739935-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001113525.2(ZNF276):​c.*1689C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0965 in 1,605,564 control chromosomes in the GnomAD database, including 8,244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1015 hom., cov: 33)
  • Exomes 𝑓: 0.095 (7229 hom.)
• Consequence: ZNF276 NM_001113525.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: 0.0200

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-89739935-C-A is Benign according to our data. Variant chr16-89739935-C-A is described in ClinVar as [Benign]. Clinvar id is 135540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF276	NM_001113525.2	c.*1689C>A		3_prime_UTR_variant	11/11	ENST00000443381.7	NP_001106997.1
FANCA	NM_000135.4	c.3934+59G>T		intron_variant		ENST00000389301.8	NP_000126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF276	ENST00000443381.7	c.*1689C>A		3_prime_UTR_variant	11/11	1	NM_001113525.2	ENSP00000415836.2
FANCA	ENST00000389301.8	c.3934+59G>T		intron_variant		1	NM_000135.4	ENSP00000373952.3

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16288 AN: 152126 Hom.: 1010 Cov.: 33

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0561

Gnomad ASJ AF: 0.0792

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0716

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0931

Gnomad OTH AF: 0.0975

GnomAD3 exomes AF: 0.0954 AC: 23782 AN: 249270 Hom.: 1526 AF XY: 0.0956 AC XY: 12875 AN XY: 134742

Gnomad AFR exome AF: 0.150

Gnomad AMR exome AF: 0.0306

Gnomad ASJ exome AF: 0.0759

Gnomad EAS exome AF: 0.234

Gnomad SAS exome AF: 0.113

Gnomad FIN exome AF: 0.0724

Gnomad NFE exome AF: 0.0870

Gnomad OTH exome AF: 0.0783

GnomAD4 exome AF: 0.0954 AC: 138574 AN: 1453320 Hom.: 7229 Cov.: 32 AF XY: 0.0958 AC XY: 69088 AN XY: 721400

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.0340

Gnomad4 ASJ exome AF: 0.0751

Gnomad4 EAS exome AF: 0.165

Gnomad4 SAS exome AF: 0.111

Gnomad4 FIN exome AF: 0.0703

Gnomad4 NFE exome AF: 0.0938

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.107 AC: 16313 AN: 152244 Hom.: 1015 Cov.: 33 AF XY: 0.105 AC XY: 7799 AN XY: 74428

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.0559

Gnomad4 ASJ AF: 0.0792

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.0716

Gnomad4 NFE AF: 0.0931

Gnomad4 OTH AF: 0.0979

Alfa AF: 0.0701 Hom.: 138

Bravo AF: 0.107

Asia WGS AF: 0.169 AC: 587 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 02, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.66

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: rs11647746; hg19: chr16-89806343; COSMIC: COSV57065776; COSMIC: COSV57065776;