22-45967859-A-G

Position:

• chr22-45967859-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT7B	NM_058238.3	c.71+8825T>C		intron_variant		ENST00000339464.9	NP_478679.1
WNT7B	NM_001410806.1	c.83+4296T>C		intron_variant			NP_001397735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT7B	ENST00000339464.9	c.71+8825T>C		intron_variant		1	NM_058238.3	ENSP00000341032.4

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

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.385

Alfa AF: 0.397 Hom.: 11377

Bravo AF: 0.405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.74
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs10453441; hg19: chr22-46363739; COSMIC: COSV59749675;