rs11246234

Positions:

• chr11-645336-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021008.4(DEAF1):​c.1594-682C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,584 control chromosomes in the GnomAD database, including 12,463 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 0.40 (12463 hom., cov: 31)
• Consequence: DEAF1 NM_021008.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.632

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEAF1	NM_021008.4	c.1594-682C>T		intron_variant		ENST00000382409.4
DEAF1	NM_001293634.1	c.1369-682C>T		intron_variant
DEAF1	NM_001367390.1	c.868-682C>T		intron_variant
DEAF1	XM_047426251.1	c.868-682C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEAF1	ENST00000382409.4	c.1594-682C>T		intron_variant		1	NM_021008.4	P1

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60650 AN: 151466 Hom.: 12464 Cov.: 31

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.421

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.400 AC: 60673 AN: 151584 Hom.: 12463 Cov.: 31 AF XY: 0.402 AC XY: 29745 AN XY: 74032

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.417

Alfa AF: 0.408 Hom.: 2133

Bravo AF: 0.391

Asia WGS AF: 0.461 AC: 1605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.5
DANN	Benign	0.75

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: rs11246234; hg19: chr11-645336;