rs4487645

Variant names:

• chr7-21898622-C-A
• rs4487645
• NM_001277115.2:c.13050-714C>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 55 publications found

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 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 7

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.13050-714C>A		intron_variant	Intron 79 of 81	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.13050-714C>A		intron_variant	Intron 79 of 81	5	NM_001277115.2	ENSP00000475939.1
DNAH11	ENST00000479878.1	n.421-714C>A		intron_variant	Intron 2 of 4	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

African (AFR) AF: 0.105 AC: 4379 AN: 41526

American (AMR) AF: 0.276 AC: 4213 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1378 AN: 3464

East Asian (EAS) AF: 0.162 AC: 836 AN: 5160

South Asian (SAS) AF: 0.231 AC: 1114 AN: 4814

European-Finnish (FIN) AF: 0.335 AC: 3536 AN: 10570

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.332 AC: 22571 AN: 67970

Other (OTH) AF: 0.263 AC: 556 AN: 2112

Alfa AF: 0.313 Hom.: 23517

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
PhyloP100		-1.5
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: rs4487645; hg19: chr7-21938240;