rs10615

chr11-653968-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_021008.4(DEAF1):c.1587A>G(p.Gln529=) 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:2
• Conservation: PhyloP100: 1.51

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEAF1	NM_021008.4	c.1587A>G	p.Gln529=	synonymous_variant	11/12	ENST00000382409.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEAF1	ENST00000382409.4	c.1587A>G	p.Gln529=	synonymous_variant	11/12	1	NM_021008.4	P1

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

GnomAD3 exomes AF: 0.150 AC: 37582 AN: 251242 Hom.: 4506 AF XY: 0.144 AC XY: 19609 AN XY: 135794

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 SAS exome AF: 0.141

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

Gnomad4 AFR exome AF: 0.562

Gnomad4 AMR exome AF: 0.0929

Gnomad4 ASJ exome AF: 0.138

Gnomad4 EAS exome AF: 0.201

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.162

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

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.0970

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.227

Alfa AF: 0.140 Hom.: 3506

Bravo AF: 0.259

Asia WGS AF: 0.209 AC: 728 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	12
Dann	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs10615; hg19: chr11-653968; COSMIC: COSV58606888;