rs8040756

Variant names:

• chr15-55506401-G-A
• rs8040756
• NM_130810.4:c.-256+1721C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-55506401-G-A
• chr15-55506401-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130810.4(DNAAF4):​c.-256+1721C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,026 control chromosomes in the GnomAD database, including 9,573 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 (9573 hom., cov: 32)
• Consequence: DNAAF4 NM_130810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• Publications: 11 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 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 25

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Ambry Genetics, G2P
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF4	NM_130810.4	c.-256+1721C>T		intron_variant	Intron 1 of 9	ENST00000321149.7	NP_570722.2
DNAAF4	NM_001033560.2	c.-256+1721C>T		intron_variant	Intron 1 of 8		NP_001028732.1
DNAAF4	NM_001033559.3	c.-256+1721C>T		intron_variant	Intron 1 of 8		NP_001028731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000321149.7	c.-256+1721C>T		intron_variant	Intron 1 of 9	1	NM_130810.4	ENSP00000323275.3

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43017 AN: 151906 Hom.: 9536 Cov.: 32

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.284 AC: 43111 AN: 152026 Hom.: 9573 Cov.: 32 AF XY: 0.279 AC XY: 20732 AN XY: 74290

African (AFR) AF: 0.626 AC: 25932 AN: 41444

American (AMR) AF: 0.166 AC: 2534 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 630 AN: 3468

East Asian (EAS) AF: 0.190 AC: 979 AN: 5162

South Asian (SAS) AF: 0.256 AC: 1230 AN: 4812

European-Finnish (FIN) AF: 0.124 AC: 1317 AN: 10582

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9881 AN: 67980

Other (OTH) AF: 0.234 AC: 494 AN: 2112

Alfa AF: 0.181 Hom.: 2615

Bravo AF: 0.298

Asia WGS AF: 0.250 AC: 868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.10
DANN	Benign	0.53
PhyloP100		-0.021
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8040756; hg19: chr15-55798599;