1-225107534-T-G

Variant names:

• chr1-225107534-T-G
• rs1871570
• NM_001367479.1:c.3867+6650T>G

Variant summary

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

The NM_001367479.1(DNAH14):​c.3867+6650T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 151,954 control chromosomes in the GnomAD database, including 34,585 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 0.66 (34585 hom., cov: 31)
• Consequence: DNAH14 NM_001367479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98
• Publications: 2 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367479.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH14	NM_001367479.1	MANE Select	c.3867+6650T>G		intron	N/A	NP_001354408.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH14	ENST00000682510.1	MANE Select	c.3867+6650T>G		intron	N/A	ENSP00000508305.1
	DNAH14	ENST00000430092.5	TSL:5	c.3867+6650T>G		intron	N/A	ENSP00000414402.1
	DNAH14	ENST00000439375.6	TSL:5	c.3867+6650T>G		intron	N/A	ENSP00000392061.2

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99794 AN: 151836 Hom.: 34525 Cov.: 31

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.630

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

GnomAD4 genome AF: 0.658 AC: 99911 AN: 151954 Hom.: 34585 Cov.: 31 AF XY: 0.658 AC XY: 48842 AN XY: 74260

African (AFR) AF: 0.873 AC: 36198 AN: 41474

American (AMR) AF: 0.656 AC: 10008 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1702 AN: 3470

East Asian (EAS) AF: 0.846 AC: 4376 AN: 5170

South Asian (SAS) AF: 0.693 AC: 3330 AN: 4806

European-Finnish (FIN) AF: 0.538 AC: 5668 AN: 10544

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.540 AC: 36701 AN: 67916

Other (OTH) AF: 0.632 AC: 1332 AN: 2106

Alfa AF: 0.581 Hom.: 11831

Bravo AF: 0.677

Asia WGS AF: 0.800 AC: 2781 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.32
PhyloP100		-2.0
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: rs1871570; hg19: chr1-225295236;