NM_130810.4:c.271+1092C>G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130810.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF4	NM_130810.4	MANE Select	c.271+1092C>G		intron	N/A	NP_570722.2	Q8WXU2-1
	DNAAF4	NM_001033560.2		c.271+1092C>G		intron	N/A	NP_001028732.1	Q8WXU2-2
	DNAAF4	NM_001033559.3		c.271+1092C>G		intron	N/A	NP_001028731.1	Q8WXU2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF4	ENST00000321149.7	TSL:1 MANE Select	c.271+1092C>G		intron	N/A	ENSP00000323275.3	Q8WXU2-1
	DNAAF4	ENST00000448430.6	TSL:1	c.271+1092C>G		intron	N/A	ENSP00000403412.2	Q8WXU2-2
	DNAAF4	ENST00000457155.6	TSL:1	c.271+1092C>G		intron	N/A	ENSP00000402640.2	Q8WXU2-3

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

African (AFR) AF: 0.0162 AC: 672 AN: 41522

American (AMR) AF: 0.0464 AC: 709 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0585 AC: 203 AN: 3470

East Asian (EAS) AF: 0.145 AC: 751 AN: 5174

South Asian (SAS) AF: 0.138 AC: 664 AN: 4822

European-Finnish (FIN) AF: 0.0339 AC: 359 AN: 10600

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.0585 AC: 3982 AN: 68014

Other (OTH) AF: 0.0510 AC: 108 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.73
DANN	Benign	0.41
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16976349; hg19: chr15-55788818;