rs16976349

Variant names:

• chr15-55496620-G-C
• rs16976349
• NM_130810.4:c.271+1092C>G

Variant summary

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

The NM_130810.4(DNAAF4):​c.271+1092C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 152,212 control chromosomes in the GnomAD database, including 260 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 0.049 (260 hom., cov: 32)
• Consequence: DNAAF4 NM_130810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285

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-CCPG1 (HGNC:43019): (DNAAF4-CCPG1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring dyslexia susceptibility 1 candidate 1 (DYX1C1) and cell cycle progression 1 (CCPG1) genes on chromosome 15. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

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 = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF4	NM_130810.4	c.271+1092C>G		intron_variant	Intron 3 of 9	ENST00000321149.7	NP_570722.2
DNAAF4	NM_001033560.2	c.271+1092C>G		intron_variant	Intron 3 of 8		NP_001028732.1
DNAAF4	NM_001033559.3	c.271+1092C>G		intron_variant	Intron 3 of 8		NP_001028731.1
DNAAF4-CCPG1	NR_037923.1	n.526+1092C>G		intron_variant	Intron 2 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000321149.7	c.271+1092C>G		intron_variant	Intron 3 of 9	1	NM_130810.4	ENSP00000323275.3

Frequencies

GnomAD3 genomes AF: 0.0495 AC: 7525 AN: 152096 Hom.: 259 Cov.: 32

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0466

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0339

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0586

Gnomad OTH AF: 0.0492

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

GnomAD4 genome AF: 0.0494 AC: 7519 AN: 152212 Hom.: 260 Cov.: 32 AF XY: 0.0494 AC XY: 3678 AN XY: 74412

Gnomad4 AFR AF: 0.0162

Gnomad4 AMR AF: 0.0464

Gnomad4 ASJ AF: 0.0585

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.0339

Gnomad4 NFE AF: 0.0585

Gnomad4 OTH AF: 0.0510

Alfa AF: 0.0483 Hom.: 27

Bravo AF: 0.0473

Asia WGS AF: 0.118 AC: 410 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	0.73
DANN	Benign	0.41

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: rs16976349; hg19: chr15-55788818;