chr11-653968-T-C

Variant names:

• chr11-653968-T-C
• rs10615
• NM_021008.4:c.1587A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_021008.4(DEAF1):​c.1587A>G​(p.Gln529Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,613,254 control chromosomes in the GnomAD database, including 23,850 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (7249 hom., cov: 30)
  • Exomes 𝑓: 0.13 (16601 hom.)
• Consequence: DEAF1 NM_021008.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.51
• Publications: 13 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 11-653968-T-C is Benign according to our data. Variant chr11-653968-T-C is described in ClinVar as Benign. ClinVar VariationId is 585774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.51 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.545 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.1587A>G	p.Gln529Gln	synonymous	Exon 11 of 12	NP_066288.2
	DEAF1	NM_001440884.1		c.1458A>G	p.Gln486Gln	synonymous	Exon 10 of 11	NP_001427813.1
	DEAF1	NM_001293634.2		c.1362A>G	p.Gln454Gln	synonymous	Exon 10 of 11	NP_001280563.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEAF1	ENST00000382409.4	TSL:1 MANE Select	c.1587A>G	p.Gln529Gln	synonymous	Exon 11 of 12	ENSP00000371846.3	O75398-1
	DEAF1	ENST00000527170.5	TSL:1	n.948A>G		non_coding_transcript_exon	Exon 8 of 10	ENSP00000431563.1	H0YCH1
	DEAF1	ENST00000882097.1		c.1713A>G	p.Gln571Gln	synonymous	Exon 12 of 13	ENSP00000552156.1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36648 AN: 151720 Hom.: 7231 Cov.: 30

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.0530

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0970

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.228

GnomAD2 exomes AF: 0.150 AC: 37582 AN: 251242 AF XY: 0.144

Gnomad AFR exome AF: 0.558

Gnomad AMR exome AF: 0.0861

Gnomad ASJ exome AF: 0.135

Gnomad EAS exome AF: 0.228

Gnomad FIN exome AF: 0.0982

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.139

GnomAD4 exome AF: 0.131 AC: 191242 AN: 1461416 Hom.: 16601 Cov.: 33 AF XY: 0.130 AC XY: 94627 AN XY: 726996

African (AFR) AF: 0.562 AC: 18814 AN: 33474

American (AMR) AF: 0.0929 AC: 4154 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 3612 AN: 26136

East Asian (EAS) AF: 0.201 AC: 7981 AN: 39694

South Asian (SAS) AF: 0.144 AC: 12400 AN: 86242

European-Finnish (FIN) AF: 0.101 AC: 5358 AN: 53290

Middle Eastern (MID) AF: 0.158 AC: 910 AN: 5762

European-Non Finnish (NFE) AF: 0.115 AC: 128230 AN: 1111732

Other (OTH) AF: 0.162 AC: 9783 AN: 60372

GnomAD4 genome AF: 0.242 AC: 36696 AN: 151838 Hom.: 7249 Cov.: 30 AF XY: 0.238 AC XY: 17667 AN XY: 74224

African (AFR) AF: 0.551 AC: 22762 AN: 41300

American (AMR) AF: 0.143 AC: 2179 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 461 AN: 3468

East Asian (EAS) AF: 0.208 AC: 1073 AN: 5150

South Asian (SAS) AF: 0.146 AC: 704 AN: 4824

European-Finnish (FIN) AF: 0.0970 AC: 1026 AN: 10576

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7899 AN: 67956

Other (OTH) AF: 0.227 AC: 479 AN: 2108

Alfa AF: 0.159 Hom.: 10949

Bravo AF: 0.259

Asia WGS AF: 0.209 AC: 728 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.63
PhyloP100		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs10615; hg19: chr11-653968; COSMIC: COSV58606888;