rs4722063

Positions:

• chr7-21853886-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001277115.2(DNAH11):​c.11062-429T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 152,056 control chromosomes in the GnomAD database, including 21,305 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 0.50 (21305 hom., cov: 32)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.11062-429T>C		intron_variant		ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.11062-429T>C		intron_variant		5	NM_001277115.2	ENSP00000475939.1
DNAH11	ENST00000421290.1	n.245-429T>C		intron_variant		4
DNAH11	ENST00000607413.5	n.325-429T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75678 AN: 151938 Hom.: 21317 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.498 AC: 75671 AN: 152056 Hom.: 21305 Cov.: 32 AF XY: 0.488 AC XY: 36249 AN XY: 74338

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.538

Alfa AF: 0.544 Hom.: 4072

Bravo AF: 0.477

Asia WGS AF: 0.294 AC: 1027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Benign	0.81

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: rs4722063; hg19: chr7-21893504;