22-45923156-G-T

Variant names:

• chr22-45923156-G-T
• rs60537690
• NM_058238.3:c.750C>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_058238.3(WNT7B):​c.750C>A​(p.Thr250Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00324 in 1,613,562 control chromosomes in the GnomAD database, including 141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (72 hom., cov: 34)
  • Exomes 𝑓: 0.0017 (69 hom.)
• Consequence: WNT7B NM_058238.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.51
• Publications: 0 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 22-45923156-G-T is Benign according to our data. Variant chr22-45923156-G-T is described in ClinVar as Benign. ClinVar VariationId is 786386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.51 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0595 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT7B	NM_058238.3	MANE Select	c.750C>A	p.Thr250Thr	synonymous	Exon 4 of 4	NP_478679.1	P56706
	WNT7B	NM_001410806.1		c.762C>A	p.Thr254Thr	synonymous	Exon 4 of 4	NP_001397735.1	A8K0G1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT7B	ENST00000339464.9	TSL:1 MANE Select	c.750C>A	p.Thr250Thr	synonymous	Exon 4 of 4	ENSP00000341032.4	P56706
	WNT7B	ENST00000409496.7	TSL:2	c.762C>A	p.Thr254Thr	synonymous	Exon 4 of 4	ENSP00000386546.3	A8K0G1
	WNT7B	ENST00000410089.5	TSL:5	c.702C>A	p.Thr234Thr	synonymous	Exon 4 of 4	ENSP00000386781.1	B8A595

Frequencies

GnomAD3 genomes AF: 0.0176 AC: 2675 AN: 152256 Hom.: 72 Cov.: 34

Gnomad AFR AF: 0.0616

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00460 AC: 1154 AN: 250870 AF XY: 0.00312

Gnomad AFR exome AF: 0.0611

Gnomad AMR exome AF: 0.00370

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000212

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00175 AC: 2553 AN: 1461188 Hom.: 69 Cov.: 32 AF XY: 0.00146 AC XY: 1058 AN XY: 726918

African (AFR) AF: 0.0584 AC: 1954 AN: 33480

American (AMR) AF: 0.00382 AC: 171 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52756

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5768

European-Non Finnish (NFE) AF: 0.000146 AC: 162 AN: 1111984

Other (OTH) AF: 0.00391 AC: 236 AN: 60388

GnomAD4 genome AF: 0.0176 AC: 2681 AN: 152374 Hom.: 72 Cov.: 34 AF XY: 0.0168 AC XY: 1251 AN XY: 74504

African (AFR) AF: 0.0615 AC: 2559 AN: 41590

American (AMR) AF: 0.00503 AC: 77 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68034

Other (OTH) AF: 0.0104 AC: 22 AN: 2112

Alfa AF: 0.00728 Hom.: 12

Bravo AF: 0.0199

Asia WGS AF: 0.00462 AC: 17 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.69
PhyloP100		2.5
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: rs60537690; hg19: chr22-46319036;