Genetic Variant NM_001037954.4:c.1972-45C>G (chr11-112018911-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.838

Publications

7 publications found

Variant links:

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]

DIXDC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 link	c.1972-45C>G		intron_variant	Intron 19 of 19	ENST00000440460.7	NP_001033043.1	Q155Q3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIXDC1	ENST00000440460.7 link	c.1972-45C>G		intron_variant	Intron 19 of 19	1	NM_001037954.4	ENSP00000394352.3		Q155Q3-1

Frequencies

GnomAD3 genomes

AF:

0.501

AC:

76070

AN:

151972

Hom.:

21390

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.430

AC:

104580

AN:

243088

AF XY:

0.420

show subpopulations

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 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.:

AF XY:

0.393

AC XY:

272126

AN XY:

692988

show subpopulations

African (AFR)

AF:

0.793

AC:

25193

AN:

31756

American (AMR)

AF:

0.442

AC:

19294

AN:

43604

Ashkenazi Jewish (ASJ)

AF:

0.301

AC:

7680

AN:

25518

East Asian (EAS)

AF:

0.567

AC:

22236

AN:

39202

South Asian (SAS)

AF:

0.417

AC:

35090

AN:

84168

European-Finnish (FIN)

AF:

0.430

AC:

22740

AN:

52934

Middle Eastern (MID)

AF:

0.420

AC:

2192

AN:

5214

European-Non Finnish (NFE)

AF:

0.370

AC:

386108

AN:

1043440

Other (OTH)

AF:

0.407

AC:

23462

AN:

57686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

15322

30644

45966

61288

76610

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12190

24380

36570

48760

60950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.501

AC:

76182

AN:

152090

Hom.:

21444

Cov.:

AF XY:

0.504

AC XY:

37462

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.776

AC:

32198

AN:

41502

American (AMR)

AF:

0.416

AC:

6348

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.299

AC:

1036

AN:

3468

East Asian (EAS)

AF:

0.584

AC:

3024

AN:

5180

South Asian (SAS)

AF:

0.418

AC:

2017

AN:

4824

European-Finnish (FIN)

AF:

0.438

AC:

4620

AN:

10536

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.373

AC:

25371

AN:

67986

Other (OTH)

AF:

0.442

AC:

934

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1721

3443

5164

6886

8607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

652

1304

1956

2608

3260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.46

PhyloP100

-0.84

Mutation Taster

=12/88

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over