11-674259-G-C

Position:

• chr11-674259-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• 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/exons	MANE	Protein	UniProt
DEAF1	NM_021008.4	c.1503+277C>G		intron_variant		ENST00000382409.4	NP_066288.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEAF1	ENST00000382409.4	c.1503+277C>G		intron_variant		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

Gnomad4 AFR exome AF: 0.277

Gnomad4 AMR exome AF: 0.563

Gnomad4 ASJ exome AF: 0.582

Gnomad4 EAS exome AF: 0.730

Gnomad4 SAS exome AF: 0.580

Gnomad4 FIN exome AF: 0.523

Gnomad4 NFE exome AF: 0.554

Gnomad4 OTH exome AF: 0.544

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

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.510

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

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: rs4073590; hg19: chr11-674259;