rs191404781

Variant names:

• chr16-89739087-G-A
• rs191404781
• NM_001113525.2:c.*841G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-89739087-G-A
• chr16-89739087-G-C
• chr16-89739087-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001113525.2(ZNF276):​c.*841G>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 0.00103 in 1,613,836 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00091 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (1 hom.)
• Consequence: ZNF276 NM_001113525.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter P:1 B:1
• Conservation: PhyloP100: -1.42
• Publications: 1 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: Laboratory for Molecular Medicine, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, G2P
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0069179535).
• BP6: Variant 16-89739087-G-A is Benign according to our data. Variant chr16-89739087-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 255265.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF276	NM_001113525.2	MANE Select	c.*841G>A		3_prime_UTR	Exon 11 of 11	NP_001106997.1
	FANCA	NM_000135.4	MANE Select	c.4167+46C>T		intron	N/A	NP_000126.2
	ZNF276	NR_110122.2		n.2841G>A		non_coding_transcript_exon	Exon 11 of 11

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF276	ENST00000443381.7	TSL:1 MANE Select	c.*841G>A		3_prime_UTR	Exon 11 of 11	ENSP00000415836.2
	ZNF276	ENST00000289816.9	TSL:1	c.*841G>A		3_prime_UTR	Exon 11 of 11	ENSP00000289816.5
	FANCA	ENST00000389301.8	TSL:1 MANE Select	c.4167+46C>T		intron	N/A	ENSP00000373952.3

Frequencies

GnomAD3 genomes AF: 0.000907 AC: 138 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00151

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000993 AC: 249 AN: 250828 AF XY: 0.000922

Gnomad AFR exome AF: 0.000619

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.000744

Gnomad NFE exome AF: 0.00167

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.00105 AC: 1529 AN: 1461510 Hom.: 1 Cov.: 35 AF XY: 0.00102 AC XY: 741 AN XY: 727026

African (AFR) AF: 0.000239 AC: 8 AN: 33476

American (AMR) AF: 0.000246 AC: 11 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26128

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39696

South Asian (SAS) AF: 0.000858 AC: 74 AN: 86230

European-Finnish (FIN) AF: 0.000900 AC: 48 AN: 53314

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.00121 AC: 1342 AN: 1111806

Other (OTH) AF: 0.000696 AC: 42 AN: 60376

GnomAD4 genome AF: 0.000906 AC: 138 AN: 152326 Hom.: 0 Cov.: 33 AF XY: 0.000873 AC XY: 65 AN XY: 74488

African (AFR) AF: 0.000313 AC: 13 AN: 41570

American (AMR) AF: 0.000719 AC: 11 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00151 AC: 103 AN: 68032

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000383 Hom.: 0

Bravo AF: 0.000722

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.000682 AC: 3

ESP6500EA AF: 0.00128 AC: 11

ExAC AF: 0.00120 AC: 146

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00136

EpiControl AF: 0.00136

ClinVar

Significance: Likely benign

Submissions summary: Pathogenic:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

Feb 28, 2020

Leiden Open Variation Database

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: curation

Curator: Arleen D. Auerbach. Submitter to LOVD: Johan den Dunnen.

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.0
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.40	T
MetaRNN	Benign	0.0069	T
PhyloP100		-1.4
PROVEAN	Benign	-1.1	N
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.0040	D
MVP		0.82
GERP RS		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs191404781; hg19: chr16-89805495; COSMIC: COSV57068604; COSMIC: COSV57068604;