NM_004625.4:c.571-10759G>A

Variant names:

• chr3-13830182-C-T
• rs6778046
• NM_004625.4:c.571-10759G>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.571-10759G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 151,892 control chromosomes in the GnomAD database, including 38,251 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 0.70 (38251 hom., cov: 31)
• Consequence: WNT7A NM_004625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT7A	NM_004625.4	c.571-10759G>A		intron_variant	Intron 3 of 3	ENST00000285018.5	NP_004616.2
WNT7A	XM_011534091.3	c.370-10759G>A		intron_variant	Intron 4 of 4		XP_011532393.1
WNT7A	XM_047448863.1	c.370-10759G>A		intron_variant	Intron 3 of 3		XP_047304819.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT7A	ENST00000285018.5	c.571-10759G>A		intron_variant	Intron 3 of 3	1	NM_004625.4	ENSP00000285018.4

Frequencies

GnomAD3 genomes AF: 0.698 AC: 105990 AN: 151774 Hom.: 38204 Cov.: 31

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.653

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

GnomAD4 genome AF: 0.699 AC: 106098 AN: 151892 Hom.: 38251 Cov.: 31 AF XY: 0.698 AC XY: 51807 AN XY: 74194

African (AFR) AF: 0.878 AC: 36377 AN: 41448

American (AMR) AF: 0.629 AC: 9599 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2191 AN: 3470

East Asian (EAS) AF: 0.904 AC: 4652 AN: 5148

South Asian (SAS) AF: 0.730 AC: 3506 AN: 4806

European-Finnish (FIN) AF: 0.601 AC: 6325 AN: 10516

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.607 AC: 41227 AN: 67942

Other (OTH) AF: 0.658 AC: 1384 AN: 2102

Alfa AF: 0.682 Hom.: 11840

Bravo AF: 0.710

Asia WGS AF: 0.809 AC: 2818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.72
PhyloP100		0.040
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: rs6778046; hg19: chr3-13871679;