Variant 14-54955599-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_007086.4(WDHD1):c.3012C>T(p.Thr1004=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00515 in 1,591,530 control chromosomes in the GnomAD database, including 372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 199 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 173 hom. )

Consequence

WDHD1
NM_007086.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.605

Variant links:

Genes affected

WDHD1 (HGNC:23170): (WD repeat and HMG-box DNA binding protein 1) The protein encoded by this gene contains multiple N-terminal WD40 domains and a C-terminal high mobility group (HMG) box. WD40 domains are found in a variety of eukaryotic proteins and may function as adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly. HMG boxes are found in many eukaryotic proteins involved in chromatin assembly, transcription and replication. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

WDHD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 14-54955599-G-A is Benign according to our data. Variant chr14-54955599-G-A is described in ClinVar as [Benign]. Clinvar id is 776841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.605 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
WDHD1	NM_007086.4 linkuse as main transcript	c.3012C>T	p.Thr1004=	synonymous_variant	24/26	ENST00000360586.8
WDHD1	NM_001008396.3 linkuse as main transcript	c.2643C>T	p.Thr881=	synonymous_variant	23/25
WDHD1	XM_006720012.2 linkuse as main transcript	c.3006C>T	p.Thr1002=	synonymous_variant	24/26
WDHD1	XM_011536373.3 linkuse as main transcript	c.1923C>T	p.Thr641=	synonymous_variant	15/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDHD1	ENST00000360586.8 linkuse as main transcript	c.3012C>T	p.Thr1004=	synonymous_variant	24/26	1	NM_007086.4	P1	O75717-1
WDHD1	ENST00000420358.2 linkuse as main transcript	c.2643C>T	p.Thr881=	synonymous_variant	23/25	5			O75717-2
WDHD1	ENST00000567693.1 linkuse as main transcript	c.*1462C>T		3_prime_UTR_variant, NMD_transcript_variant	12/14	2

Frequencies

GnomAD3 genomes

AF:

0.0287

AC:

4362

AN:

151894

Hom.:

199

Cov.:

show subpopulations

Gnomad AFR

AF:

0.100

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0112

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.00673

AC:

1556

AN:

231292

Hom.:

AF XY:

0.00469

AC XY:

590

AN XY:

125766

show subpopulations

Gnomad AFR exome

AF:

0.0967

Gnomad AMR exome

AF:

0.00382

Gnomad ASJ exome

AF:

0.000206

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000148

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000196

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00265

AC:

3819

AN:

1439518

Hom.:

173

Cov.:

AF XY:

0.00229

AC XY:

1643

AN XY:

716076

show subpopulations

Gnomad4 AFR exome

AF:

0.0988

Gnomad4 AMR exome

AF:

0.00455

Gnomad4 ASJ exome

AF:

0.000117

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000158

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000987

Gnomad4 OTH exome

AF:

0.00617

GnomAD4 genome

AF:

0.0288

AC:

4376

AN:

152012

Hom.:

199

Cov.:

AF XY:

0.0277

AC XY:

2059

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.100

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.0157

Alfa

AF:

0.0132

Hom.:

Bravo

AF:

0.0329

Asia WGS

AF:

0.00636

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.2

DANN

Benign

0.54

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

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