11-674094-G-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000255158 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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

Gnomad4 AFR exome AF: 0.252

Gnomad4 AMR exome AF: 0.560

Gnomad4 ASJ exome AF: 0.566

Gnomad4 EAS exome AF: 0.706

Gnomad4 SAS exome AF: 0.546

Gnomad4 FIN exome AF: 0.504

Gnomad4 NFE exome AF: 0.533

Gnomad4 OTH exome AF: 0.521

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

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.727

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.509

Alfa AF: 0.502 Hom.: 2925

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4073591; hg19: chr11-674094;