rs11647746

Variant names:

• chr16-89739935-C-A
• rs11647746
• NM_001113525.2:c.*1689C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-89739935-C-A
• chr16-89739935-C-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate 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
• Publications: 13 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.032).
• BP6: Variant 16-89739935-C-A is Benign according to our data. Variant chr16-89739935-C-A is described in ClinVar as Benign. ClinVar VariationId 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.

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.*1689C>A		3_prime_UTR	Exon 11 of 11	NP_001106997.1	Q8N554-1
	FANCA	NM_000135.4	MANE Select	c.3934+59G>T		intron	N/A	NP_000126.2	O15360-1
	ZNF276	NM_152287.4		c.*1689C>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.*1689C>A		3_prime_UTR	Exon 11 of 11	ENSP00000415836.2	Q8N554-1
	ZNF276	ENST00000289816.9	TSL:1	c.*1689C>A		3_prime_UTR	Exon 11 of 11	ENSP00000289816.5	Q8N554-2
	FANCA	ENST00000389301.8	TSL:1 MANE Select	c.3934+59G>T		intron	N/A	ENSP00000373952.3	O15360-1

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

GnomAD2 exomes AF: 0.0954 AC: 23782 AN: 249270 AF XY: 0.0956

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 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

African (AFR) AF: 0.149 AC: 4949 AN: 33260

American (AMR) AF: 0.0340 AC: 1505 AN: 44298

Ashkenazi Jewish (ASJ) AF: 0.0751 AC: 1943 AN: 25856

East Asian (EAS) AF: 0.165 AC: 6526 AN: 39474

South Asian (SAS) AF: 0.111 AC: 9550 AN: 85866

European-Finnish (FIN) AF: 0.0703 AC: 3738 AN: 53196

Middle Eastern (MID) AF: 0.0588 AC: 337 AN: 5732

European-Non Finnish (NFE) AF: 0.0938 AC: 103737 AN: 1105682

Other (OTH) AF: 0.105 AC: 6289 AN: 59956

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

African (AFR) AF: 0.147 AC: 6090 AN: 41542

American (AMR) AF: 0.0559 AC: 855 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0792 AC: 275 AN: 3472

East Asian (EAS) AF: 0.223 AC: 1154 AN: 5172

South Asian (SAS) AF: 0.126 AC: 609 AN: 4830

European-Finnish (FIN) AF: 0.0716 AC: 759 AN: 10606

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0931 AC: 6331 AN: 68010

Other (OTH) AF: 0.0979 AC: 207 AN: 2114

Alfa AF: 0.0937 Hom.: 1431

Bravo AF: 0.107

Asia WGS AF: 0.169 AC: 587 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.66
PhyloP100		0.020
PromoterAI		-0.028	Neutral
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: rs11647746; hg19: chr16-89806343; COSMIC: COSV57065776; COSMIC: COSV57065776;