rs1061646

Variant names:

• chr16-89739569-G-A
• rs1061646
• NM_001113525.2:c.*1323G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-89739569-G-A
• chr16-89739569-G-C
• chr16-89739569-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001113525.2(ZNF276):​c.*1323G>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 0.355 in 1,550,080 control chromosomes in the GnomAD database, including 107,219 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (14131 hom., cov: 32)
  • Exomes 𝑓: 0.35 (93088 hom.)
• Consequence: ZNF276 NM_001113525.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.398
• Publications: 36 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 16-89739569-G-A is Benign according to our data. Variant chr16-89739569-G-A is described in ClinVar as Benign. ClinVar VariationId is 255264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.723 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.*1323G>A		3_prime_UTR	Exon 11 of 11	NP_001106997.1	Q8N554-1
	FANCA	NM_000135.4	MANE Select	c.3935-16C>T		intron	N/A	NP_000126.2	O15360-1
	ZNF276	NM_152287.4		c.*1323G>A		3_prime_UTR	Exon 11 of 11	NP_689500.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF276	ENST00000443381.7	TSL:1 MANE Select	c.*1323G>A		3_prime_UTR	Exon 11 of 11	ENSP00000415836.2	Q8N554-1
	ZNF276	ENST00000289816.9	TSL:1	c.*1323G>A		3_prime_UTR	Exon 11 of 11	ENSP00000289816.5	Q8N554-2
	FANCA	ENST00000389301.8	TSL:1 MANE Select	c.3935-16C>T		intron	N/A	ENSP00000373952.3	O15360-1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62320 AN: 151940 Hom.: 14112 Cov.: 32

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.361

GnomAD2 exomes AF: 0.425 AC: 65869 AN: 155154 AF XY: 0.417

Gnomad AFR exome AF: 0.546

Gnomad AMR exome AF: 0.613

Gnomad ASJ exome AF: 0.234

Gnomad EAS exome AF: 0.725

Gnomad FIN exome AF: 0.393

Gnomad NFE exome AF: 0.293

Gnomad OTH exome AF: 0.365

GnomAD4 exome AF: 0.349 AC: 487419 AN: 1398022 Hom.: 93088 Cov.: 35 AF XY: 0.350 AC XY: 241644 AN XY: 689600

African (AFR) AF: 0.546 AC: 17226 AN: 31578

American (AMR) AF: 0.596 AC: 21291 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 5987 AN: 25176

East Asian (EAS) AF: 0.808 AC: 28870 AN: 35736

South Asian (SAS) AF: 0.475 AC: 37634 AN: 79218

European-Finnish (FIN) AF: 0.388 AC: 18872 AN: 48650

Middle Eastern (MID) AF: 0.265 AC: 1503 AN: 5672

European-Non Finnish (NFE) AF: 0.311 AC: 335409 AN: 1078310

Other (OTH) AF: 0.356 AC: 20627 AN: 57978

GnomAD4 genome AF: 0.410 AC: 62394 AN: 152058 Hom.: 14131 Cov.: 32 AF XY: 0.422 AC XY: 31343 AN XY: 74330

African (AFR) AF: 0.538 AC: 22319 AN: 41450

American (AMR) AF: 0.485 AC: 7411 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 821 AN: 3468

East Asian (EAS) AF: 0.743 AC: 3821 AN: 5146

South Asian (SAS) AF: 0.492 AC: 2369 AN: 4818

European-Finnish (FIN) AF: 0.395 AC: 4187 AN: 10596

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20377 AN: 67976

Other (OTH) AF: 0.367 AC: 775 AN: 2110

Alfa AF: 0.344 Hom.: 16380

Bravo AF: 0.425

Asia WGS AF: 0.610 AC: 2120 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Fanconi anemia complementation group A (2)
-	-	1	Fanconi anemia (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.0
DANN	Benign	0.44
PhyloP100		0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs1061646; hg19: chr16-89805977; COSMIC: COSV57068489; COSMIC: COSV57068489;