rs117691319

Positions:

chr11-686888-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_021008.4(DEAF1):c.774C>T(p.Tyr258Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,614,214 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 12 hom., cov: 33)

Exomes 𝑓: 0.012 ( 111 hom. )

Consequence

DEAF1
NM_021008.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.352

Variant links:

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 links:

DEAF1 (HGNC:):

DEAF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 11-686888-G-A is Benign according to our data. Variant chr11-686888-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 447242.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.352 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00997 (1519/152346) while in subpopulation NFE AF= 0.0141 (959/68032). AF 95% confidence interval is 0.0134. There are 12 homozygotes in gnomad4. There are 782 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEAF1	NM_021008.4 linkuse as main transcript	c.774C>T	p.Tyr258Tyr	synonymous_variant	5/12	ENST00000382409.4	NP_066288.2	O75398-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEAF1	ENST00000382409.4 linkuse as main transcript	c.774C>T	p.Tyr258Tyr	synonymous_variant	5/12	1	NM_021008.4	ENSP00000371846.3		O75398-1

Frequencies

GnomAD3 genomes

AF:

0.00998

AC:

1519

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00680

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0249

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0141

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.0103

AC:

2594

AN:

251178

Hom.:

AF XY:

0.0104

AC XY:

1418

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.00544

Gnomad ASJ exome

AF:

0.0150

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00167

Gnomad FIN exome

AF:

0.0251

Gnomad NFE exome

AF:

0.0138

Gnomad OTH exome

AF:

0.00946

GnomAD4 exome

AF:

0.0119

AC:

17416

AN:

1461868

Hom.:

111

Cov.:

AF XY:

0.0117

AC XY:

8521

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00188

Gnomad4 AMR exome

AF:

0.00530

Gnomad4 ASJ exome

AF:

0.0145

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00205

Gnomad4 FIN exome

AF:

0.0265

Gnomad4 NFE exome

AF:

0.0131

Gnomad4 OTH exome

AF:

0.00950

GnomAD4 genome

AF:

0.00997

AC:

1519

AN:

152346

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

782

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00226

Gnomad4 AMR

AF:

0.00679

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.0249

Gnomad4 NFE

AF:

0.0141

Gnomad4 OTH

AF:

0.00992

Alfa

AF:

0.0120

Hom.:

Bravo

AF:

0.00833

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0152

EpiControl

AF:

0.0138

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	DEAF1: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jul 07, 2017

- -

Intellectual disability, autosomal dominant 24;C4310683:Intellectual disability-epilepsy-extrapyramidal syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jan 21, 2022

- -

DEAF1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 08, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

1.1

DANN

Benign

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over