Variant chr16-71230658-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PVS1_ModerateBP6_Very_StrongBA1

The ENST00000288168.14(HYDIN):c.28+2T>C variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,535,720 control chromosomes in the GnomAD database, including 17,121 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1845 hom., cov: 32)

Exomes 𝑓: 0.13 ( 15276 hom. )

Consequence

HYDIN
ENST00000288168.14 splice_donor

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.517

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.018824609 fraction of the gene.

BP6

Variant 16-71230658-A-G is Benign according to our data. Variant chr16-71230658-A-G is described in ClinVar as [Benign]. Clinvar id is 402960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HYDIN	NM_001270974.2 linkuse as main transcript	c.-120T>C		5_prime_UTR_variant	1/86	ENST00000393567.7
HYDIN	NM_001198543.1 linkuse as main transcript	c.28+2T>C		splice_donor_variant
HYDIN	NM_001198542.1 linkuse as main transcript	c.30T>C	p.Gly10=	synonymous_variant	1/19
HYDIN	NM_017558.5 linkuse as main transcript	c.-120T>C		5_prime_UTR_variant	1/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HYDIN	ENST00000393567.7 linkuse as main transcript	c.-120T>C		5_prime_UTR_variant	1/86	5	NM_001270974.2	P1	Q4G0P3-1

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18576

AN:

151844

Hom.:

1825

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0287

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.315

Gnomad ASJ

AF:

0.0859

Gnomad EAS

AF:

0.291

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.0860

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.129

GnomAD3 exomes

AF:

0.198

AC:

27062

AN:

136650

Hom.:

4318

AF XY:

0.185

AC XY:

13732

AN XY:

74218

show subpopulations

Gnomad AFR exome

AF:

0.0252

Gnomad AMR exome

AF:

0.474

Gnomad ASJ exome

AF:

0.0812

Gnomad EAS exome

AF:

0.303

Gnomad SAS exome

AF:

0.157

Gnomad FIN exome

AF:

0.158

Gnomad NFE exome

AF:

0.116

Gnomad OTH exome

AF:

0.164

GnomAD4 exome

AF:

0.130

AC:

179822

AN:

1383756

Hom.:

15276

Cov.:

AF XY:

0.130

AC XY:

88883

AN XY:

682822

show subpopulations

Gnomad4 AFR exome

AF:

0.0211

Gnomad4 AMR exome

AF:

0.455

Gnomad4 ASJ exome

AF:

0.0811

Gnomad4 EAS exome

AF:

0.327

Gnomad4 SAS exome

AF:

0.161

Gnomad4 FIN exome

AF:

0.149

Gnomad4 NFE exome

AF:

0.115

Gnomad4 OTH exome

AF:

0.124

GnomAD4 genome

AF:

0.122

AC:

18606

AN:

151964

Hom.:

1845

Cov.:

AF XY:

0.128

AC XY:

9495

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.0286

Gnomad4 AMR

AF:

0.317

Gnomad4 ASJ

AF:

0.0859

Gnomad4 EAS

AF:

0.290

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.149

Gnomad4 NFE

AF:

0.118

Gnomad4 OTH

AF:

0.136

Alfa

AF:

0.124

Hom.:

1721

Bravo

AF:

0.135

TwinsUK

AF:

0.113

AC:

420

ALSPAC

AF:

0.117

AC:

451

ExAC

AF:

0.106

AC:

1872

Asia WGS

AF:

0.239

AC:

829

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes: 375/2178=17.21% -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.49

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.050

MutationTaster

Benign

1.0

P;P;P;P;P;P

GERP RS

-0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over