rs12042076

Variant names:

• chr1-225289844-A-C
• rs12042076
• NM_001367479.1:c.8272-41A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-225289844-A-C
• chr1-225289844-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-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 rank	MANE	Protein	UniProt
DNAH14	NM_001367479.1	c.8272-41A>C		intron_variant	Intron 54 of 85	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1	c.8272-41A>C		intron_variant	Intron 54 of 85		NM_001367479.1	ENSP00000508305.1

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

GnomAD2 exomes AF: 0.359 AC: 14930 AN: 41572 AF XY: 0.364

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 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

African (AFR) AF: 0.140 AC: 3252 AN: 23176

American (AMR) AF: 0.389 AC: 4130 AN: 10624

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 5262 AN: 15500

East Asian (EAS) AF: 0.479 AC: 13336 AN: 27866

South Asian (SAS) AF: 0.440 AC: 10770 AN: 24468

European-Finnish (FIN) AF: 0.388 AC: 14732 AN: 37944

Middle Eastern (MID) AF: 0.261 AC: 1086 AN: 4162

European-Non Finnish (NFE) AF: 0.359 AC: 326345 AN: 908890

Other (OTH) AF: 0.346 AC: 15269 AN: 44094

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

African (AFR) AF: 0.156 AC: 6468 AN: 41512

American (AMR) AF: 0.377 AC: 5752 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1124 AN: 3468

East Asian (EAS) AF: 0.443 AC: 2291 AN: 5166

South Asian (SAS) AF: 0.440 AC: 2123 AN: 4826

European-Finnish (FIN) AF: 0.374 AC: 3953 AN: 10568

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.358 AC: 24325 AN: 67898

Other (OTH) AF: 0.313 AC: 660 AN: 2110

Alfa AF: 0.340 Hom.: 34009

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
PhyloP100		-0.33
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: rs12042076; hg19: chr1-225477546; COSMIC: COSV59901676;