rs1004330

Variant names:

• chr16-70999060-G-A
• rs1004330
• NM_001270974.2:c.3645-6850C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001270974.2(HYDIN):​c.3645-6850C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,860 control chromosomes in the GnomAD database, including 8,790 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 (8790 hom., cov: 29)
• Consequence: HYDIN NM_001270974.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 1 publications found

Genes affected

HYDIN (HGNC:19368): (HYDIN axonemal central pair apparatus protein) This gene encodes a protein that may be involved in cilia motility. Mutations in this gene cause of autosomal recessive primary ciliary dyskinesia-5, a disorder characterized by the accumulation of cerebrospinal fluid within the ventricles of the brain. A duplicate copy of this gene has been found in humans on chromosome 1. [provided by RefSeq, Jan 2013]

HYDIN Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 5

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, ClinGen, G2P
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000305278 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYDIN	NM_001270974.2	c.3645-6850C>T		intron_variant	Intron 23 of 85	ENST00000393567.7	NP_001257903.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYDIN	ENST00000393567.7	c.3645-6850C>T		intron_variant	Intron 23 of 85	5	NM_001270974.2	ENSP00000377197.2
HYDIN	ENST00000393552.6	n.2355-6850C>T		intron_variant	Intron 14 of 17	1		ENSP00000463767.1
ENSG00000305278	ENST00000809994.1	n.190+11306G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47511 AN: 151744 Hom.: 8752 Cov.: 29

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.313 AC: 47601 AN: 151860 Hom.: 8790 Cov.: 29 AF XY: 0.315 AC XY: 23386 AN XY: 74244

African (AFR) AF: 0.503 AC: 20868 AN: 41454

American (AMR) AF: 0.408 AC: 6221 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 846 AN: 3466

East Asian (EAS) AF: 0.231 AC: 1192 AN: 5156

South Asian (SAS) AF: 0.278 AC: 1331 AN: 4784

European-Finnish (FIN) AF: 0.201 AC: 2122 AN: 10554

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14170 AN: 67876

Other (OTH) AF: 0.298 AC: 626 AN: 2104

Alfa AF: 0.264 Hom.: 1846

Bravo AF: 0.338

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.65
PhyloP100		0.074
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1004330; hg19: chr16-71032963;