12-48968996-T-G

Variant names:

• chr12-48968996-T-G
• rs833834
• NM_003394.4:c.338-677A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003394.4(WNT10B):​c.338-677A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.942 in 454,650 control chromosomes in the GnomAD database, including 203,289 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 0.90 (62213 hom., cov: 30)
  • Exomes 𝑓: 0.96 (141076 hom.)
• Consequence: WNT10B NM_003394.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

Genes affected

WNT10B (HGNC:12775): (Wnt family member 10B) The WNT gene family consists of structurally related genes which 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 a member of the WNT gene family. It may be involved in breast cancer, and its protein signaling is likely a molecular switch that governs adipogenesis. This protein is 96% identical to the mouse Wnt10b protein at the amino acid level. This gene is clustered with another family member, WNT1, in the chromosome 12q13 region. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT10B	NM_003394.4	c.338-677A>C		intron_variant	Intron 3 of 4	ENST00000301061.9	NP_003385.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT10B	ENST00000301061.9	c.338-677A>C		intron_variant	Intron 3 of 4	1	NM_003394.4	ENSP00000301061.4
WNT10B	ENST00000407467.5	c.338-677A>C		intron_variant	Intron 3 of 5	2		ENSP00000384691.1
WNT10B	ENST00000403957.5	c.338-677A>C		intron_variant	Intron 3 of 5	5		ENSP00000385980.1
WNT10B	ENST00000413630.1	c.372+114A>C		intron_variant	Intron 3 of 3	5		ENSP00000398473.1

Frequencies

GnomAD3 genomes AF: 0.897 AC: 136221 AN: 151896 Hom.: 62194 Cov.: 30

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.941

Gnomad ASJ AF: 0.963

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.972

Gnomad FIN AF: 0.994

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.903

GnomAD4 exome AF: 0.964 AC: 291833 AN: 302636 Hom.: 141076 AF XY: 0.966 AC XY: 164949 AN XY: 170794

Gnomad4 AFR exome AF: 0.694

Gnomad4 AMR exome AF: 0.967

Gnomad4 ASJ exome AF: 0.964

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.966

Gnomad4 FIN exome AF: 0.994

Gnomad4 NFE exome AF: 0.972

Gnomad4 OTH exome AF: 0.957

GnomAD4 genome AF: 0.897 AC: 136284 AN: 152014 Hom.: 62213 Cov.: 30 AF XY: 0.900 AC XY: 66861 AN XY: 74310

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.941

Gnomad4 ASJ AF: 0.963

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.972

Gnomad4 FIN AF: 0.994

Gnomad4 NFE AF: 0.972

Gnomad4 OTH AF: 0.904

Alfa AF: 0.904 Hom.: 4824

Bravo AF: 0.884

Asia WGS AF: 0.973 AC: 3382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.5
DANN	Benign	0.79

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: rs833834; hg19: chr12-49362779;