3-13823578-A-G

Variant names:

• chr3-13823578-A-G
• rs9840696
• NM_004625.4:c.571-4155T>C

Variant summary

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

The NM_004625.4(WNT7A):​c.571-4155T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 152,190 control chromosomes in the GnomAD database, including 38,969 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 0.71 (38969 hom., cov: 32)
• Consequence: WNT7A NM_004625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.825
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 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.571-4155T>C		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.571-4155T>C		intron	N/A	ENSP00000285018.4

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107255 AN: 152072 Hom.: 38925 Cov.: 32

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.705 AC: 107359 AN: 152190 Hom.: 38969 Cov.: 32 AF XY: 0.706 AC XY: 52519 AN XY: 74388

African (AFR) AF: 0.877 AC: 36442 AN: 41540

American (AMR) AF: 0.642 AC: 9818 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2202 AN: 3468

East Asian (EAS) AF: 0.890 AC: 4601 AN: 5170

South Asian (SAS) AF: 0.757 AC: 3652 AN: 4822

European-Finnish (FIN) AF: 0.629 AC: 6667 AN: 10594

Middle Eastern (MID) AF: 0.699 AC: 204 AN: 292

European-Non Finnish (NFE) AF: 0.614 AC: 41722 AN: 67996

Other (OTH) AF: 0.660 AC: 1393 AN: 2112

Alfa AF: 0.641 Hom.: 40088

Bravo AF: 0.714

Asia WGS AF: 0.816 AC: 2840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.66
PhyloP100		-0.82
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: rs9840696; hg19: chr3-13865075;