NM_021008.4:c.1594-682C>T

Variant names:

• chr11-645336-G-A
• rs11246234
• NM_021008.4:c.1594-682C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021008.4(DEAF1):​c.1594-682C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,584 control chromosomes in the GnomAD database, including 12,463 homozygotes. 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: 𝑓 0.40 (12463 hom., cov: 31)
• Consequence: DEAF1 NM_021008.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.632
• Publications: 7 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• intellectual disability-epilepsy-extrapyramidal syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

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.1594-682C>T		intron	N/A	NP_066288.2
	DEAF1	NM_001440883.1		c.1504-682C>T		intron	N/A	NP_001427812.1
	DEAF1	NM_001440884.1		c.1465-682C>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.1594-682C>T		intron	N/A	ENSP00000371846.3
	DEAF1	ENST00000527170.5	TSL:1	n.*154-682C>T		intron	N/A	ENSP00000431563.1
	DEAF1	ENST00000882097.1		c.1720-682C>T		intron	N/A	ENSP00000552156.1

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60650 AN: 151466 Hom.: 12464 Cov.: 31

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.421

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.400 AC: 60673 AN: 151584 Hom.: 12463 Cov.: 31 AF XY: 0.402 AC XY: 29745 AN XY: 74032

African (AFR) AF: 0.321 AC: 13230 AN: 41240

American (AMR) AF: 0.354 AC: 5387 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1500 AN: 3472

East Asian (EAS) AF: 0.556 AC: 2870 AN: 5164

South Asian (SAS) AF: 0.504 AC: 2423 AN: 4806

European-Finnish (FIN) AF: 0.432 AC: 4515 AN: 10452

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29278 AN: 67924

Other (OTH) AF: 0.417 AC: 876 AN: 2102

Alfa AF: 0.381 Hom.: 4670

Bravo AF: 0.391

Asia WGS AF: 0.461 AC: 1605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.5
DANN	Benign	0.75
PhyloP100		-0.63
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: rs11246234; hg19: chr11-645336;