1-225107534-T-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH14	NM_001367479.1	c.3867+6650T>G		intron_variant	Intron 23 of 85	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1	c.3867+6650T>G		intron_variant	Intron 23 of 85		NM_001367479.1	ENSP00000508305.1
DNAH14	ENST00000430092.5	c.3867+6650T>G		intron_variant	Intron 23 of 83	5		ENSP00000414402.1
DNAH14	ENST00000439375.6	c.3867+6650T>G		intron_variant	Intron 22 of 82	5		ENSP00000392061.2
DNAH14	ENST00000445597.6	c.3051+21745T>G		intron_variant	Intron 16 of 60	5		ENSP00000409472.2

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

Gnomad4 AFR AF: 0.873

Gnomad4 AMR AF: 0.656

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.846

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.632

Alfa AF: 0.567 Hom.: 8999

Bravo AF: 0.677

Asia WGS AF: 0.800 AC: 2781 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	1.7
DANN	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs1871570; hg19: chr1-225295236;