rs16976351

Variant names:

• chr15-55496634-C-T
• rs16976351
• NM_130810.4:c.271+1078G>A

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+1078G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,142 control chromosomes in the GnomAD database, including 7,001 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 0.21 (7001 hom., cov: 32)
• Consequence: DNAAF4 NM_130810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.510
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF4	NM_130810.4	c.271+1078G>A		intron_variant	Intron 3 of 9	ENST00000321149.7	NP_570722.2
DNAAF4	NM_001033560.2	c.271+1078G>A		intron_variant	Intron 3 of 8		NP_001028732.1
DNAAF4	NM_001033559.3	c.271+1078G>A		intron_variant	Intron 3 of 8		NP_001028731.1
DNAAF4-CCPG1	NR_037923.1	n.526+1078G>A		intron_variant	Intron 2 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000321149.7	c.271+1078G>A		intron_variant	Intron 3 of 9	1	NM_130810.4	ENSP00000323275.3

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32203 AN: 152024 Hom.: 6985 Cov.: 32

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0829

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0752

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.212 AC: 32264 AN: 152142 Hom.: 7001 Cov.: 32 AF XY: 0.207 AC XY: 15435 AN XY: 74390

African (AFR) AF: 0.560 AC: 23235 AN: 41458

American (AMR) AF: 0.111 AC: 1692 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 387 AN: 3472

East Asian (EAS) AF: 0.0104 AC: 54 AN: 5184

South Asian (SAS) AF: 0.104 AC: 504 AN: 4830

European-Finnish (FIN) AF: 0.0829 AC: 879 AN: 10606

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0752 AC: 5114 AN: 67996

Other (OTH) AF: 0.169 AC: 357 AN: 2110

Alfa AF: 0.110 Hom.: 1002

Bravo AF: 0.228

Asia WGS AF: 0.0920 AC: 323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.37
DANN	Benign	0.56
PhyloP100		-0.51
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: rs16976351; hg19: chr15-55788832;