16-89738853-A-G

Position:

• chr16-89738853-A-G

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.*607A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 1,613,960 control chromosomes in the GnomAD database, including 353,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (41730 hom., cov: 35)
  • Exomes 𝑓: 0.65 (311444 hom.)
• Consequence: ZNF276 NM_001113525.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -6.74

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-89738853-A-G is Benign according to our data. Variant chr16-89738853-A-G is described in ClinVar as [Benign]. Clinvar id is 255266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89738853-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF276	NM_001113525.2	c.*607A>G		3_prime_UTR_variant	11/11	ENST00000443381.7	NP_001106997.1
FANCA	NM_000135.4	c.4260+29T>C		intron_variant		ENST00000389301.8	NP_000126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF276	ENST00000443381.7	c.*607A>G		3_prime_UTR_variant	11/11	1	NM_001113525.2	ENSP00000415836	P2
FANCA	ENST00000389301.8	c.4260+29T>C		intron_variant		1	NM_000135.4	ENSP00000373952	P1

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109971 AN: 152144 Hom.: 41663 Cov.: 35

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.668

GnomAD3 exomes AF: 0.702 AC: 176220 AN: 250980 Hom.: 64442 AF XY: 0.695 AC XY: 94254 AN XY: 135672

Gnomad AFR exome AF: 0.936

Gnomad AMR exome AF: 0.786

Gnomad ASJ exome AF: 0.520

Gnomad EAS exome AF: 0.987

Gnomad SAS exome AF: 0.801

Gnomad FIN exome AF: 0.695

Gnomad NFE exome AF: 0.591

Gnomad OTH exome AF: 0.644

GnomAD4 exome AF: 0.646 AC: 943666 AN: 1461698 Hom.: 311444 Cov.: 83 AF XY: 0.648 AC XY: 471318 AN XY: 727120

Gnomad4 AFR exome AF: 0.939

Gnomad4 AMR exome AF: 0.776

Gnomad4 ASJ exome AF: 0.525

Gnomad4 EAS exome AF: 0.980

Gnomad4 SAS exome AF: 0.802

Gnomad4 FIN exome AF: 0.685

Gnomad4 NFE exome AF: 0.608

Gnomad4 OTH exome AF: 0.656

GnomAD4 genome AF: 0.723 AC: 110102 AN: 152262 Hom.: 41730 Cov.: 35 AF XY: 0.731 AC XY: 54404 AN XY: 74438

Gnomad4 AFR AF: 0.928

Gnomad4 AMR AF: 0.704

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.986

Gnomad4 SAS AF: 0.823

Gnomad4 FIN AF: 0.692

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.672

Alfa AF: 0.608 Hom.: 14450

Bravo AF: 0.734

Asia WGS AF: 0.904 AC: 3142 AN: 3478

EpiCase AF: 0.583

EpiControl AF: 0.575

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 09, 2019	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Fanconi anemia complementation group A Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.050
DANN	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs1800359; hg19: chr16-89805261; COSMIC: COSV57066846; COSMIC: COSV57066846;