11-654511-G-A

Position:

• chr11-654511-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000382409.4(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 ENST00000382409.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.04

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEAF1	NM_021008.4	c.1504-460C>T		intron_variant		ENST00000382409.4	NP_066288.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEAF1	ENST00000382409.4	c.1504-460C>T		intron_variant		1	NM_021008.4	ENSP00000371846	P1

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

Gnomad4 AFR exome AF: 0.483

Gnomad4 AMR exome AF: 0.0880

Gnomad4 ASJ exome AF: 0.137

Gnomad4 EAS exome AF: 0.219

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.102

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.152

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

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.0970

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.211

Alfa AF: 0.173 Hom.: 506

Bravo AF: 0.236

Asia WGS AF: 0.205 AC: 712 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.76
DANN	Benign	0.51

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: rs7951023; hg19: chr11-654511;