1-225289844-A-C

Position:

• chr1-225289844-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367479.1(DNAH14):​c.8272-41A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,248,730 control chromosomes in the GnomAD database, including 80,775 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 0.31 (8122 hom., cov: 32)
  • Exomes 𝑓: 0.36 (72653 hom.)
• Consequence: DNAH14 NM_001367479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH14	NM_001367479.1	c.8272-41A>C		intron_variant		ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1	c.8272-41A>C		intron_variant			NM_001367479.1	ENSP00000508305	P1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47111 AN: 151886 Hom.: 8116 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.310

GnomAD3 exomes AF: 0.359 AC: 14930 AN: 41572 Hom.: 2793 AF XY: 0.364 AC XY: 7612 AN XY: 20912

Gnomad AFR exome AF: 0.136

Gnomad AMR exome AF: 0.399

Gnomad ASJ exome AF: 0.324

Gnomad EAS exome AF: 0.434

Gnomad SAS exome AF: 0.434

Gnomad FIN exome AF: 0.382

Gnomad NFE exome AF: 0.359

Gnomad OTH exome AF: 0.343

GnomAD4 exome AF: 0.359 AC: 394182 AN: 1096724 Hom.: 72653 Cov.: 18 AF XY: 0.360 AC XY: 188312 AN XY: 522904

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.389

Gnomad4 ASJ exome AF: 0.339

Gnomad4 EAS exome AF: 0.479

Gnomad4 SAS exome AF: 0.440

Gnomad4 FIN exome AF: 0.388

Gnomad4 NFE exome AF: 0.359

Gnomad4 OTH exome AF: 0.346

GnomAD4 genome AF: 0.310 AC: 47130 AN: 152006 Hom.: 8122 Cov.: 32 AF XY: 0.314 AC XY: 23340 AN XY: 74288

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.313

Alfa AF: 0.338 Hom.: 14228

Bravo AF: 0.303

Asia WGS AF: 0.450 AC: 1564 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.30
DANN	Benign	0.50

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: rs12042076; hg19: chr1-225477546; COSMIC: COSV59901676;