rs796065314

Variant names:

• chr11-46700937-C-A
• rs796065314
• NM_024741.3:c.-111C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024741.3(ZNF408):​c.-111C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000556 in 898,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: ZNF408 NM_024741.3 upstream_gene
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.791
• Publications: 1 publications found

Genes affected

ZNF408 (HGNC:20041): (zinc finger protein 408) The protein encoded by this gene contains ten tandem zinc fingers and an N-terminal SET domain, so it is likely a DNA binding protein that interacts with other proteins. In adults, the encoded protein is expressed most highly in retina. Consequently, defects in this gene have been associated with familial exudative vitreoretinopathy (FEVR) and retinitis pigmentosa (RP). [provided by RefSeq, Dec 2016]

ZNF408 Gene-Disease associations (from GenCC):

• exudative vitreoretinopathy 6

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• retinitis pigmentosa 72

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• exudative vitreoretinopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024741.3. 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
	ZNF408	NM_024741.3	MANE Select	c.-111C>A		upstream_gene	N/A	NP_079017.1
	ZNF408	NM_001184751.2		c.-177C>A		upstream_gene	N/A	NP_001171680.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF408	ENST00000311764.3	TSL:1 MANE Select	c.-111C>A		upstream_gene	N/A	ENSP00000309606.2
	ZNF408	ENST00000526410.1	TSL:3	n.-94C>A		upstream_gene	N/A
	ZNF408	ENST00000531866.1	TSL:2	n.-93C>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000556 AC: 5 AN: 898844 Hom.: 0 Cov.: 12 AF XY: 0.00000860 AC XY: 4 AN XY: 465310

African (AFR) AF: 0.00 AC: 0 AN: 22700

American (AMR) AF: 0.00 AC: 0 AN: 41480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20000

East Asian (EAS) AF: 0.00 AC: 0 AN: 37190

South Asian (SAS) AF: 0.0000580 AC: 4 AN: 68918

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48720

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3042

European-Non Finnish (NFE) AF: 0.00000163 AC: 1 AN: 615216

Other (OTH) AF: 0.00 AC: 0 AN: 41578

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Exudative vitreoretinopathy 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.57
DANN	Benign	0.43
PhyloP100		-0.79
PromoterAI		0.042	Neutral

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: rs796065314; hg19: chr11-46722487;