rs235987

Positions:

• chr16-71215443-C-T

Variant summary

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

The NM_001270974.2(HYDIN):​c.-24+15119G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,118 control chromosomes in the GnomAD database, including 2,929 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 0.17 (2929 hom., cov: 31)
• Consequence: HYDIN NM_001270974.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.332

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HYDIN	NM_001270974.2	c.-24+15119G>A		intron_variant		ENST00000393567.7
HYDIN	NM_001198542.1	c.58+15187G>A		intron_variant
HYDIN	NM_001198543.1	c.28+15217G>A		intron_variant
HYDIN	NM_017558.5	c.-24+15119G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HYDIN	ENST00000393567.7	c.-24+15119G>A		intron_variant		5	NM_001270974.2	P1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26222 AN: 152000 Hom.: 2932 Cov.: 31

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.0457

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.172 AC: 26214 AN: 152118 Hom.: 2929 Cov.: 31 AF XY: 0.175 AC XY: 13010 AN XY: 74344

Gnomad4 AFR AF: 0.0427

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.0458

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.211

Alfa AF: 0.232 Hom.: 8705

Bravo AF: 0.161

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.2
DANN	Benign	0.80

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: rs235987; hg19: chr16-71249346;