rs16976343

Positions:

• chr15-55495055-T-C

Variant summary

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

The NM_130810.4(DNAAF4):​c.271+2657A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 151,636 control chromosomes in the GnomAD database, including 9,738 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 0.28 (9738 hom., cov: 30)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: DNAAF4 NM_130810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500

Genes affected

DNAAF4 (HGNC:21493): (dynein axonemal assembly factor 4) This gene encodes a tetratricopeptide repeat domain-containing protein. The encoded protein interacts with estrogen receptors and the heat shock proteins, Hsp70 and Hsp90. An homologous protein in rat has been shown to function in neuronal migration in the developing neocortex. A chromosomal translocation involving this gene is associated with a susceptibility to developmental dyslexia. Mutations in this gene are associated with deficits in reading and spelling. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream cell cycle progression 1 (CCPG1) gene. [provided by RefSeq, Mar 2011]

DNAAF4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF4	NM_130810.4	c.271+2657A>G		intron_variant		ENST00000321149.7	NP_570722.2
DNAAF4	NM_001033560.2	c.271+2657A>G		intron_variant			NP_001028732.1
DNAAF4	NM_001033559.3	c.271+2657A>G		intron_variant			NP_001028731.1
DNAAF4-CCPG1	NR_037923.1	n.526+2657A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000321149.7	c.271+2657A>G		intron_variant		1	NM_130810.4	ENSP00000323275.3

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42531 AN: 151510 Hom.: 9699 Cov.: 30

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.167

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.250 AC: 2 AN: 8 Hom.: 0 AF XY: 0.333 AC XY: 2 AN XY: 6

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.281 AC: 42625 AN: 151628 Hom.: 9738 Cov.: 30 AF XY: 0.277 AC XY: 20526 AN XY: 74118

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.236

Alfa AF: 0.161 Hom.: 4221

Bravo AF: 0.296

Asia WGS AF: 0.247 AC: 857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.3
DANN	Benign	0.77

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: rs16976343; hg19: chr15-55787253;