rs650461

Variant names:

• chr11-112018911-C-G
• rs650461
• NM_001037954.4:c.1972-45C>G

Variant summary

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

The NM_001037954.4(DIXDC1):​c.1972-45C>G 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 1,535,612 control chromosomes in the GnomAD database, including 132,460 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 0.50 (21444 hom., cov: 32)
  • Exomes 𝑓: 0.39 (111016 hom.)
• Consequence: DIXDC1 NM_001037954.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.838

Genes affected

DIXDC1 (HGNC:23695): (DIX domain containing 1) The protein encoded by this gene is a positive regulator of the Wnt signaling pathway. The encoded protein is found associated with gamma tubulin at the centrosome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIXDC1	NM_001037954.4	c.1972-45C>G		intron_variant	Intron 19 of 19	ENST00000440460.7	NP_001033043.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIXDC1	ENST00000440460.7	c.1972-45C>G		intron_variant	Intron 19 of 19	1	NM_001037954.4	ENSP00000394352.3

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76070 AN: 151972 Hom.: 21390 Cov.: 32

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.442

GnomAD3 exomes AF: 0.430 AC: 104580 AN: 243088 Hom.: 23920 AF XY: 0.420 AC XY: 55571 AN XY: 132170

Gnomad AFR exome AF: 0.788

Gnomad AMR exome AF: 0.445

Gnomad ASJ exome AF: 0.307

Gnomad EAS exome AF: 0.593

Gnomad SAS exome AF: 0.415

Gnomad FIN exome AF: 0.439

Gnomad NFE exome AF: 0.366

Gnomad OTH exome AF: 0.384

GnomAD4 exome AF: 0.393 AC: 543995 AN: 1383522 Hom.: 111016 Cov.: 20 AF XY: 0.393 AC XY: 272126 AN XY: 692988

Gnomad4 AFR exome AF: 0.793

Gnomad4 AMR exome AF: 0.442

Gnomad4 ASJ exome AF: 0.301

Gnomad4 EAS exome AF: 0.567

Gnomad4 SAS exome AF: 0.417

Gnomad4 FIN exome AF: 0.430

Gnomad4 NFE exome AF: 0.370

Gnomad4 OTH exome AF: 0.407

GnomAD4 genome AF: 0.501 AC: 76182 AN: 152090 Hom.: 21444 Cov.: 32 AF XY: 0.504 AC XY: 37462 AN XY: 74314

Gnomad4 AFR AF: 0.776

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.442

Alfa AF: 0.423 Hom.: 2745

Bravo AF: 0.516

Asia WGS AF: 0.480 AC: 1672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.46
DANN	Benign	0.46

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: rs650461; hg19: chr11-111889635; COSMIC: COSV59461612; COSMIC: COSV59461612;