rs35303725

chr11-674638-C-T

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.1401G>A(p.Ala467=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 1,614,138 control chromosomes in the GnomAD database, including 536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (34 hom., cov: 33)
  • Exomes 𝑓: 0.019 (502 hom.)
• Consequence: DEAF1 NM_021008.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.78

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 11-674638-C-T is Benign according to our data. Variant chr11-674638-C-T is described in ClinVar as [Benign]. Clinvar id is 585771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.78 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEAF1	NM_021008.4	c.1401G>A	p.Ala467=	synonymous_variant	10/12	ENST00000382409.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEAF1	ENST00000382409.4	c.1401G>A	p.Ala467=	synonymous_variant	10/12	1	NM_021008.4	P1
	ENST00000527799.1	n.843+379C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2198 AN: 152208 Hom.: 34 Cov.: 33

Gnomad AFR AF: 0.00439

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0181

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.0550

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0170

Gnomad OTH AF: 0.0258

GnomAD3 exomes AF: 0.0208 AC: 5240 AN: 251460 Hom.: 116 AF XY: 0.0244 AC XY: 3318 AN XY: 135906

Gnomad AFR exome AF: 0.00369

Gnomad AMR exome AF: 0.0120

Gnomad ASJ exome AF: 0.0428

Gnomad EAS exome AF: 0.0158

Gnomad SAS exome AF: 0.0652

Gnomad FIN exome AF: 0.00264

Gnomad NFE exome AF: 0.0162

Gnomad OTH exome AF: 0.0235

GnomAD4 exome AF: 0.0193 AC: 28244 AN: 1461812 Hom.: 502 Cov.: 34 AF XY: 0.0210 AC XY: 15238 AN XY: 727212

Gnomad4 AFR exome AF: 0.00394

Gnomad4 AMR exome AF: 0.0133

Gnomad4 ASJ exome AF: 0.0394

Gnomad4 EAS exome AF: 0.00831

Gnomad4 SAS exome AF: 0.0656

Gnomad4 FIN exome AF: 0.00279

Gnomad4 NFE exome AF: 0.0168

Gnomad4 OTH exome AF: 0.0231

GnomAD4 genome AF: 0.0144 AC: 2196 AN: 152326 Hom.: 34 Cov.: 33 AF XY: 0.0146 AC XY: 1090 AN XY: 74496

Gnomad4 AFR AF: 0.00440

Gnomad4 AMR AF: 0.0180

Gnomad4 ASJ AF: 0.0421

Gnomad4 EAS AF: 0.0152

Gnomad4 SAS AF: 0.0547

Gnomad4 FIN AF: 0.00226

Gnomad4 NFE AF: 0.0171

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0170 Hom.: 13

Bravo AF: 0.0145

Asia WGS AF: 0.0270 AC: 94 AN: 3478

EpiCase AF: 0.0179

EpiControl AF: 0.0188

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 18, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 29, 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	-0.69
Cadd	Benign	0.093
Dann	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs35303725; hg19: chr11-674638; COSMIC: COSV58610018;