chr3-13863503-C-T

Variant names:

• chr3-13863503-C-T
• rs9828013
• NM_004625.4:c.299-8700G>A

Variant summary

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

The NM_004625.4(WNT7A):​c.299-8700G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 151,836 control chromosomes in the GnomAD database, including 28,326 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 0.59 (28326 hom., cov: 32)
• Consequence: WNT7A NM_004625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453
• Publications: 5 publications found

Genes affected

WNT7A (HGNC:12786): (Wnt family member 7A) This gene is a member of the WNT gene family, which consists of structurally related genes that encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is involved in the development of the anterior-posterior axis in the female reproductive tract, and also plays a critical role in uterine smooth muscle pattering and maintenance of adult uterine function. Mutations in this gene are associated with Fuhrmann and Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndromes. [provided by RefSeq, Jul 2008]

WNT7A Gene-Disease associations (from GenCC):

• Fuhrmann syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• phocomelia, Schinzel type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004625.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT7A	NM_004625.4	MANE Select	c.299-8700G>A		intron	N/A	NP_004616.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT7A	ENST00000285018.5	TSL:1 MANE Select	c.299-8700G>A		intron	N/A	ENSP00000285018.4
	WNT7A	ENST00000489346.1	TSL:3	n.*165G>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89283 AN: 151718 Hom.: 28276 Cov.: 32

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.589 AC: 89402 AN: 151836 Hom.: 28326 Cov.: 32 AF XY: 0.589 AC XY: 43684 AN XY: 74162

African (AFR) AF: 0.819 AC: 33924 AN: 41414

American (AMR) AF: 0.524 AC: 7999 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1726 AN: 3466

East Asian (EAS) AF: 0.812 AC: 4193 AN: 5164

South Asian (SAS) AF: 0.626 AC: 3008 AN: 4804

European-Finnish (FIN) AF: 0.425 AC: 4454 AN: 10486

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.475 AC: 32268 AN: 67926

Other (OTH) AF: 0.568 AC: 1198 AN: 2110

Alfa AF: 0.518 Hom.: 27664

Bravo AF: 0.605

Asia WGS AF: 0.695 AC: 2419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.4
DANN	Benign	0.86
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9828013; hg19: chr3-13905000;