rs7951023

Variant names:

• chr11-654511-G-A
• rs7951023
• NM_021008.4:c.1504-460C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021008.4(DEAF1):​c.1504-460C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 454,842 control chromosomes in the GnomAD database, including 9,712 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (6121 hom., cov: 30)
  • Exomes 𝑓: 0.13 (3591 hom.)
• Consequence: DEAF1 NM_021008.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.04
• Publications: 6 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, Ambry Genetics, Orphanet
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-654511-G-A is Benign according to our data. Variant chr11-654511-G-A is described in ClinVar as Benign. ClinVar VariationId is 585770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.479 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.1504-460C>T		intron	N/A	NP_066288.2
	DEAF1	NM_001440883.1		c.1504-9857C>T		intron	N/A	NP_001427812.1
	DEAF1	NM_001440884.1		c.1375-460C>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.1504-460C>T		intron	N/A	ENSP00000371846.3	O75398-1
	DEAF1	ENST00000527170.5	TSL:1	n.865-460C>T		intron	N/A	ENSP00000431563.1	H0YCH1
	DEAF1	ENST00000882097.1		c.1630-460C>T		intron	N/A	ENSP00000552156.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33289 AN: 150932 Hom.: 6114 Cov.: 30

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0970

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.212

GnomAD4 exome AF: 0.131 AC: 39819 AN: 303792 Hom.: 3591 AF XY: 0.131 AC XY: 22689 AN XY: 173004

African (AFR) AF: 0.483 AC: 4150 AN: 8592

American (AMR) AF: 0.0880 AC: 2400 AN: 27274

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 1472 AN: 10782

East Asian (EAS) AF: 0.219 AC: 2015 AN: 9218

South Asian (SAS) AF: 0.139 AC: 8303 AN: 59732

European-Finnish (FIN) AF: 0.102 AC: 1265 AN: 12374

Middle Eastern (MID) AF: 0.145 AC: 401 AN: 2774

European-Non Finnish (NFE) AF: 0.111 AC: 17648 AN: 158822

Other (OTH) AF: 0.152 AC: 2165 AN: 14224

GnomAD4 genome AF: 0.221 AC: 33318 AN: 151050 Hom.: 6121 Cov.: 30 AF XY: 0.217 AC XY: 16050 AN XY: 73852

African (AFR) AF: 0.485 AC: 19670 AN: 40574

American (AMR) AF: 0.134 AC: 2039 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 458 AN: 3462

East Asian (EAS) AF: 0.202 AC: 1040 AN: 5140

South Asian (SAS) AF: 0.141 AC: 675 AN: 4804

European-Finnish (FIN) AF: 0.0970 AC: 1026 AN: 10572

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7853 AN: 67962

Other (OTH) AF: 0.211 AC: 444 AN: 2104

Alfa AF: 0.185 Hom.: 600

Bravo AF: 0.236

Asia WGS AF: 0.205 AC: 712 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.76
DANN	Benign	0.51
PhyloP100		-3.0
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: rs7951023; hg19: chr11-654511;