rs4487645

Positions:

• chr7-21898622-C-A
• chr7-21898622-C-T

Variant summary

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

The NM_001277115.2(DNAH11):​c.13050-714C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,082 control chromosomes in the GnomAD database, including 5,863 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 0.26 (5863 hom., cov: 32)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

Genes affected

DNAH11 (HGNC:2942): (dynein axonemal heavy chain 11) This gene encodes a ciliary outer dynein arm protein and is a member of the dynein heavy chain family. It is a microtubule-dependent motor ATPase and has been reported to be involved in the movement of respiratory cilia. Mutations in this gene have been implicated in causing Kartagener Syndrome (a combination of situs inversus totalis and Primary Ciliary Dyskinesia (PCD), also called Immotile Cilia Syndrome 1 (ICS1)) and male sterility. [provided by RefSeq, Mar 2013]

DNAH11 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.13050-714C>A		intron_variant		ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.13050-714C>A		intron_variant		5	NM_001277115.2	ENSP00000475939.1
DNAH11	ENST00000479878.1	n.421-714C>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38844 AN: 151964 Hom.: 5867 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.255 AC: 38840 AN: 152082 Hom.: 5863 Cov.: 32 AF XY: 0.254 AC XY: 18914 AN XY: 74326

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.263

Alfa AF: 0.318 Hom.: 17081

Bravo AF: 0.244

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.28

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: rs4487645; hg19: chr7-21938240;