rs4073590

Variant names:

• chr11-674259-G-A
• rs4073590
• NM_021008.4:c.1503+277C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-674259-G-A
• chr11-674259-G-C
• chr11-674259-G-T

Variant summary

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

The NM_021008.4(DEAF1):​c.1503+277C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DEAF1 NM_021008.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.298
• Publications: 10 publications found

Genes affected

DEAF1 (HGNC:14677): (DEAF1 transcription factor) This gene encodes a zinc finger domain-containing protein that functions as a regulator of transcription. The encoded proteins binds to its own promoter as well as to that of several target genes. Activity of this protein is important in the regulation of embryonic development. Mutations in this gene have been found in individuals with autosomal dominant cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

DEAF1 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal dominant 24

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• intellectual disability-epilepsy-extrapyramidal syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: SD Classification: STRONG Submitted by: Illumina
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000255158 (HGNC:):

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=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021008.4. 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
	DEAF1	NM_021008.4	MANE Select	c.1503+277C>T		intron	N/A	NP_066288.2
	DEAF1	NM_001440883.1		c.1503+277C>T		intron	N/A	NP_001427812.1
	DEAF1	NM_001440884.1		c.1374+277C>T		intron	N/A	NP_001427813.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEAF1	ENST00000382409.4	TSL:1 MANE Select	c.1503+277C>T		intron	N/A	ENSP00000371846.3	O75398-1
	DEAF1	ENST00000527170.5	TSL:1	n.864+277C>T		intron	N/A	ENSP00000431563.1	H0YCH1
	DEAF1	ENST00000882097.1		c.1629+277C>T		intron	N/A	ENSP00000552156.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 301194 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 160570

African (AFR) AF: 0.00 AC: 0 AN: 8928

American (AMR) AF: 0.00 AC: 0 AN: 13936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8856

East Asian (EAS) AF: 0.00 AC: 0 AN: 16864

South Asian (SAS) AF: 0.00 AC: 0 AN: 43074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1250

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 176014

Other (OTH) AF: 0.00 AC: 0 AN: 17038

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.81
DANN	Benign	0.53
PhyloP100		0.30

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: rs4073590; hg19: chr11-674259;