chr3-13871353-C-G

Variant names:

• chr3-13871353-C-G
• rs11128663
• NM_004625.4:c.298+3594G>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.298+3594G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 151,940 control chromosomes in the GnomAD database, including 31,573 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 0.64 (31573 hom., cov: 31)
• Consequence: WNT7A NM_004625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.480
• Publications: 3 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, Orphanet, Labcorp Genetics (formerly Invitae)
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT7A	NM_004625.4	MANE Select	c.298+3594G>C		intron	N/A	NP_004616.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT7A	ENST00000285018.5	TSL:1 MANE Select	c.298+3594G>C		intron	N/A	ENSP00000285018.4	O00755
	WNT7A	ENST00000489346.1	TSL:3	n.167+3594G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96784 AN: 151822 Hom.: 31528 Cov.: 31

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.630

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

GnomAD4 genome AF: 0.638 AC: 96894 AN: 151940 Hom.: 31573 Cov.: 31 AF XY: 0.644 AC XY: 47791 AN XY: 74242

African (AFR) AF: 0.691 AC: 28639 AN: 41436

American (AMR) AF: 0.668 AC: 10210 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2064 AN: 3468

East Asian (EAS) AF: 0.939 AC: 4837 AN: 5150

South Asian (SAS) AF: 0.848 AC: 4080 AN: 4812

European-Finnish (FIN) AF: 0.542 AC: 5732 AN: 10566

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39326 AN: 67920

Other (OTH) AF: 0.635 AC: 1338 AN: 2108

Alfa AF: 0.600 Hom.: 3459

Bravo AF: 0.649

Asia WGS AF: 0.870 AC: 3024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.8
DANN	Benign	0.70
PhyloP100		0.48
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: rs11128663; hg19: chr3-13912850;