3-13846232-C-T

Variant names:

• chr3-13846232-C-T
• rs934450
• NM_004625.4:c.570+8300G>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.570+8300G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,134 control chromosomes in the GnomAD database, including 10,560 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 0.37 (10560 hom., cov: 33)
• Consequence: WNT7A NM_004625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT7A	NM_004625.4	c.570+8300G>A		intron_variant	Intron 3 of 3	ENST00000285018.5	NP_004616.2
WNT7A	XM_011534091.3	c.369+8300G>A		intron_variant	Intron 4 of 4		XP_011532393.1
WNT7A	XM_047448863.1	c.369+8300G>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.570+8300G>A		intron_variant	Intron 3 of 3	1	NM_004625.4	ENSP00000285018.4

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55660 AN: 152016 Hom.: 10538 Cov.: 33

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.379

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

GnomAD4 genome AF: 0.366 AC: 55721 AN: 152134 Hom.: 10560 Cov.: 33 AF XY: 0.367 AC XY: 27305 AN XY: 74372

African (AFR) AF: 0.469 AC: 19452 AN: 41502

American (AMR) AF: 0.344 AC: 5254 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1313 AN: 3472

East Asian (EAS) AF: 0.347 AC: 1794 AN: 5164

South Asian (SAS) AF: 0.470 AC: 2266 AN: 4822

European-Finnish (FIN) AF: 0.283 AC: 2996 AN: 10592

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21408 AN: 67970

Other (OTH) AF: 0.386 AC: 815 AN: 2114

Alfa AF: 0.248 Hom.: 701

Bravo AF: 0.372

Asia WGS AF: 0.431 AC: 1499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.10
DANN	Benign	0.73
PhyloP100		-1.2
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: rs934450; hg19: chr3-13887729;