NM_007187.5:c.216C>T

Variant names:

• chr13-41065241-C-T
• rs61740513
• NM_007187.5:c.216C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_007187.5(WBP4):​c.216C>T​(p.Ala72Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00486 in 1,609,138 control chromosomes in the GnomAD database, including 336 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (180 hom., cov: 31)
  • Exomes 𝑓: 0.0027 (156 hom.)
• Consequence: WBP4 NM_007187.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.383
• Publications: 3 publications found

Genes affected

WBP4 (HGNC:12739): (WW domain binding protein 4) This gene encodes WW domain-containing binding protein 4. The WW domain represents a small and compact globular structure that interacts with proline-rich ligands. This encoded protein is a general spliceosomal protein that may play a role in cross-intron bridging of U1 and U2 snRNPs in the spliceosomal complex A. [provided by RefSeq, Jul 2008]

WBP4 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities

  Inheritance: AR Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 13-41065241-C-T is Benign according to our data. Variant chr13-41065241-C-T is described in ClinVar as Benign. ClinVar VariationId is 768612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.383 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.089 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007187.5. 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
	WBP4	NM_007187.5	MANE Select	c.216C>T	p.Ala72Ala	synonymous	Exon 4 of 10	NP_009118.1	O75554-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WBP4	ENST00000379487.5	TSL:1 MANE Select	c.216C>T	p.Ala72Ala	synonymous	Exon 4 of 10	ENSP00000368801.3	O75554-1
	WBP4	ENST00000953016.1		c.216C>T	p.Ala72Ala	synonymous	Exon 4 of 10	ENSP00000623075.1
	WBP4	ENST00000953017.1		c.153C>T	p.Ala51Ala	synonymous	Exon 3 of 9	ENSP00000623076.1

Frequencies

GnomAD3 genomes AF: 0.0259 AC: 3866 AN: 149072 Hom.: 180 Cov.: 31

Gnomad AFR AF: 0.0915

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00830

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000420

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00968

Gnomad NFE AF: 0.000237

Gnomad OTH AF: 0.0166

GnomAD2 exomes AF: 0.00709 AC: 1774 AN: 250204 AF XY: 0.00497

Gnomad AFR exome AF: 0.0940

Gnomad AMR exome AF: 0.00541

Gnomad ASJ exome AF: 0.000696

Gnomad EAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000265

Gnomad OTH exome AF: 0.00345

GnomAD4 exome AF: 0.00270 AC: 3947 AN: 1459958 Hom.: 156 Cov.: 32 AF XY: 0.00236 AC XY: 1713 AN XY: 726228

African (AFR) AF: 0.0935 AC: 3121 AN: 33382

American (AMR) AF: 0.00599 AC: 267 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.000805 AC: 21 AN: 26082

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39634

South Asian (SAS) AF: 0.000291 AC: 25 AN: 85866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53298

Middle Eastern (MID) AF: 0.0108 AC: 62 AN: 5758

European-Non Finnish (NFE) AF: 0.0000756 AC: 84 AN: 1111060

Other (OTH) AF: 0.00607 AC: 366 AN: 60280

GnomAD4 genome AF: 0.0260 AC: 3874 AN: 149180 Hom.: 180 Cov.: 31 AF XY: 0.0247 AC XY: 1795 AN XY: 72544

African (AFR) AF: 0.0914 AC: 3695 AN: 40420

American (AMR) AF: 0.00829 AC: 124 AN: 14962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5118

South Asian (SAS) AF: 0.000421 AC: 2 AN: 4756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9690

Middle Eastern (MID) AF: 0.0105 AC: 3 AN: 286

European-Non Finnish (NFE) AF: 0.000237 AC: 16 AN: 67520

Other (OTH) AF: 0.0164 AC: 34 AN: 2070

Alfa AF: 0.0142 Hom.: 54

Bravo AF: 0.0292

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000237

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	-0.38
CADD	Benign	11
DANN	Benign	0.69
PhyloP100		0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	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: rs61740513; hg19: chr13-41639377;