11-674259-G-C

Variant names:

• chr11-674259-G-C
• rs4073590
• NM_021008.4:c.1503+277C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021008.4(DEAF1):​c.1503+277C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 452,648 control chromosomes in the GnomAD database, including 67,212 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.49 (19321 hom., cov: 33)
  • Exomes 𝑓: 0.56 (47891 hom.)
• Consequence: DEAF1 NM_021008.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.298
• Publications: 10 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, Orphanet, Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: SD Classification: STRONG Submitted by: Illumina
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000255158 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEAF1	NM_021008.4	c.1503+277C>G		intron_variant	Intron 10 of 11	ENST00000382409.4	NP_066288.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEAF1	ENST00000382409.4	c.1503+277C>G		intron_variant	Intron 10 of 11	1	NM_021008.4	ENSP00000371846.3

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73859 AN: 152002 Hom.: 19314 Cov.: 33

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.510

GnomAD4 exome AF: 0.558 AC: 167833 AN: 300528 Hom.: 47891 Cov.: 3 AF XY: 0.561 AC XY: 89903 AN XY: 160208

African (AFR) AF: 0.277 AC: 2470 AN: 8914

American (AMR) AF: 0.563 AC: 7827 AN: 13904

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 5138 AN: 8824

East Asian (EAS) AF: 0.730 AC: 12292 AN: 16832

South Asian (SAS) AF: 0.580 AC: 24943 AN: 43024

European-Finnish (FIN) AF: 0.523 AC: 7954 AN: 15194

Middle Eastern (MID) AF: 0.534 AC: 662 AN: 1240

European-Non Finnish (NFE) AF: 0.554 AC: 97294 AN: 175600

Other (OTH) AF: 0.544 AC: 9253 AN: 16996

GnomAD4 genome AF: 0.486 AC: 73908 AN: 152120 Hom.: 19321 Cov.: 33 AF XY: 0.489 AC XY: 36362 AN XY: 74364

African (AFR) AF: 0.279 AC: 11563 AN: 41484

American (AMR) AF: 0.556 AC: 8500 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2104 AN: 3470

East Asian (EAS) AF: 0.728 AC: 3772 AN: 5180

South Asian (SAS) AF: 0.586 AC: 2827 AN: 4828

European-Finnish (FIN) AF: 0.522 AC: 5527 AN: 10584

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37882 AN: 67978

Other (OTH) AF: 0.510 AC: 1075 AN: 2108

Alfa AF: 0.384 Hom.: 1116

Bravo AF: 0.481

Asia WGS AF: 0.622 AC: 2164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.57
DANN	Benign	0.46
PhyloP100		0.30
Mutation Taster		=100/0	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: rs4073590; hg19: chr11-674259;