11-674094-G-T

Variant names:

• chr11-674094-G-T
• rs4073591
• NM_021008.4:c.1503+442C>A

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+442C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 260,772 control chromosomes in the GnomAD database, including 35,224 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 (19232 hom., cov: 31)
  • Exomes 𝑓: 0.53 (15992 hom.)
• Consequence: DEAF1 NM_021008.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEAF1	NM_021008.4	c.1503+442C>A		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+442C>A		intron_variant	Intron 10 of 11	1	NM_021008.4	ENSP00000371846.3

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73655 AN: 151704 Hom.: 19225 Cov.: 31

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.509

GnomAD4 exome AF: 0.534 AC: 58170 AN: 108950 Hom.: 15992 Cov.: 0 AF XY: 0.538 AC XY: 31289 AN XY: 58134

African (AFR) AF: 0.252 AC: 873 AN: 3468

American (AMR) AF: 0.560 AC: 2776 AN: 4958

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1466 AN: 2588

East Asian (EAS) AF: 0.706 AC: 3402 AN: 4818

South Asian (SAS) AF: 0.546 AC: 10085 AN: 18478

European-Finnish (FIN) AF: 0.504 AC: 2477 AN: 4916

Middle Eastern (MID) AF: 0.506 AC: 182 AN: 360

European-Non Finnish (NFE) AF: 0.533 AC: 34082 AN: 63934

Other (OTH) AF: 0.521 AC: 2827 AN: 5430

GnomAD4 genome AF: 0.485 AC: 73704 AN: 151822 Hom.: 19232 Cov.: 31 AF XY: 0.488 AC XY: 36219 AN XY: 74166

African (AFR) AF: 0.279 AC: 11561 AN: 41434

American (AMR) AF: 0.556 AC: 8456 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2105 AN: 3472

East Asian (EAS) AF: 0.727 AC: 3736 AN: 5138

South Asian (SAS) AF: 0.585 AC: 2815 AN: 4810

European-Finnish (FIN) AF: 0.521 AC: 5493 AN: 10540

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.557 AC: 37813 AN: 67902

Other (OTH) AF: 0.509 AC: 1070 AN: 2102

Alfa AF: 0.494 Hom.: 2956

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	-0.95
CADD	Benign	1.4
DANN	Benign	0.61
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4073591; hg19: chr11-674094;