NM_058238.3:c.71+8825T>C

Variant names:

• chr22-45967859-A-G
• rs10453441
• NM_058238.3:c.71+8825T>C

Variant summary

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

The NM_058238.3(WNT7B):​c.71+8825T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,912 control chromosomes in the GnomAD database, including 12,767 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 0.40 (12767 hom., cov: 32)
• Consequence: WNT7B NM_058238.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529
• Publications: 16 publications found

Genes affected

WNT7B (HGNC:12787): (Wnt family member 7B) 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. Among members of the human WNT family, this gene product is most similar to WNT7A protein. [provided by RefSeq, Oct 2008]

WNT7B Gene-Disease associations (from GenCC):

• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058238.3. 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
	WNT7B	NM_058238.3	MANE Select	c.71+8825T>C		intron	N/A	NP_478679.1
	WNT7B	NM_001410806.1		c.83+4296T>C		intron	N/A	NP_001397735.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT7B	ENST00000339464.9	TSL:1 MANE Select	c.71+8825T>C		intron	N/A	ENSP00000341032.4
	WNT7B	ENST00000409496.7	TSL:2	c.83+4296T>C		intron	N/A	ENSP00000386546.3
	WNT7B	ENST00000410089.5	TSL:5	c.23+7686T>C		intron	N/A	ENSP00000386781.1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61410 AN: 151792 Hom.: 12768 Cov.: 32

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.404 AC: 61439 AN: 151912 Hom.: 12767 Cov.: 32 AF XY: 0.406 AC XY: 30115 AN XY: 74240

African (AFR) AF: 0.368 AC: 15234 AN: 41408

American (AMR) AF: 0.406 AC: 6197 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1299 AN: 3468

East Asian (EAS) AF: 0.688 AC: 3531 AN: 5130

South Asian (SAS) AF: 0.496 AC: 2387 AN: 4810

European-Finnish (FIN) AF: 0.398 AC: 4204 AN: 10564

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27220 AN: 67948

Other (OTH) AF: 0.385 AC: 810 AN: 2106

Alfa AF: 0.401 Hom.: 29663

Bravo AF: 0.405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.74
DANN	Benign	0.64
PhyloP100		-0.53
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: rs10453441; hg19: chr22-46363739; COSMIC: COSV59749675;