rs1480106

Variant names:

• chr1-225207574-G-A
• rs1480106
• NM_001367479.1:c.6439+354G>A

Variant summary

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

The NM_001367479.1(DNAH14):​c.6439+354G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,932 control chromosomes in the GnomAD database, including 8,722 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 0.32 (8722 hom., cov: 32)
• Consequence: DNAH14 NM_001367479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.596
• Publications: 1 publications found

Genes affected

DNAH14 (HGNC:2945): (dynein axonemal heavy chain 14) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. Two major classes of dyneins, axonemal and cytoplasmic, have been identified. DNAH14 is an axonemal dynein heavy chain (DHC) (Vaughan et al., 1996 [PubMed 8812413]).[supplied by OMIM, Mar 2008]

DNAH14 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

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 (EAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH14	NM_001367479.1	c.6439+354G>A		intron_variant	Intron 41 of 85	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1	c.6439+354G>A		intron_variant	Intron 41 of 85		NM_001367479.1	ENSP00000508305.1
DNAH14	ENST00000430092.5	c.6373+354G>A		intron_variant	Intron 40 of 83	5		ENSP00000414402.1
DNAH14	ENST00000439375.6	c.6373+354G>A		intron_variant	Intron 39 of 82	5		ENSP00000392061.2
DNAH14	ENST00000445597.6	c.5158+354G>A		intron_variant	Intron 28 of 60	5		ENSP00000409472.2

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47787 AN: 151814 Hom.: 8694 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.315 AC: 47865 AN: 151932 Hom.: 8722 Cov.: 32 AF XY: 0.317 AC XY: 23555 AN XY: 74260

African (AFR) AF: 0.445 AC: 18437 AN: 41408

American (AMR) AF: 0.372 AC: 5673 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 807 AN: 3472

East Asian (EAS) AF: 0.608 AC: 3141 AN: 5162

South Asian (SAS) AF: 0.380 AC: 1828 AN: 4812

European-Finnish (FIN) AF: 0.199 AC: 2100 AN: 10568

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15004 AN: 67948

Other (OTH) AF: 0.328 AC: 690 AN: 2106

Alfa AF: 0.266 Hom.: 773

Bravo AF: 0.336

Asia WGS AF: 0.498 AC: 1730 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	5.6
DANN	Benign	0.59
PhyloP100		0.60
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: rs1480106; hg19: chr1-225395276;