14-55017068-A-C

Position:

• chr14-55017068-A-C

Variant summary

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

The NM_007086.4(WDHD1):​c.78-3472T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.033 in 152,314 control chromosomes in the GnomAD database, including 315 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 0.033 (315 hom., cov: 32)
• Consequence: WDHD1 NM_007086.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.807

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDHD1	NM_007086.4	c.78-3472T>G		intron_variant		ENST00000360586.8	NP_009017.1
WDHD1	NM_001008396.3	c.-292-3472T>G		intron_variant			NP_001008397.1
WDHD1	XM_006720012.2	c.78-3472T>G		intron_variant			XP_006720075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDHD1	ENST00000360586.8	c.78-3472T>G		intron_variant		1	NM_007086.4	ENSP00000353793	P1
WDHD1	ENST00000420358.2	c.-292-3472T>G		intron_variant		5		ENSP00000399349
WDHD1	ENST00000455555.1	c.78-3472T>G		intron_variant		2		ENSP00000413435

Frequencies

GnomAD3 genomes AF: 0.0330 AC: 5023 AN: 152196 Hom.: 314 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0104

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0229

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

GnomAD4 genome AF: 0.0330 AC: 5027 AN: 152314 Hom.: 315 Cov.: 32 AF XY: 0.0323 AC XY: 2402 AN XY: 74480

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.0103

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0123 Hom.: 18

Bravo AF: 0.0374

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.6
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: rs28489712; hg19: chr14-55483786;