dbSNP rs10505182: CSMD3:c.9863-442C>A (chr8-112255869-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_198123.2(CSMD3):c.9863-442C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 169,220 control chromosomes in the GnomAD database, including 3,250 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 0.18 ( 2907 hom., cov: 32)

Exomes 𝑓: 0.19 ( 343 hom. )

Consequence

CSMD3
NM_198123.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.21

Publications

2 publications found

Variant links:

Genes affected

CSMD3 (HGNC:19291): (CUB and Sushi multiple domains 3) Predicted to be involved in regulation of dendrite development. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CSMD3 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CSMD3 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=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD3	NM_198123.2 link	c.9863-442C>A		intron_variant	Intron 61 of 70	ENST00000297405.10	NP_937756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD3	ENST00000297405.10 link	c.9863-442C>A		intron_variant	Intron 61 of 70	1	NM_198123.2	ENSP00000297405.5

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27046

AN:

151880

Hom.:

2908

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0667

Gnomad AMI

AF:

0.245

Gnomad AMR

AF:

0.159

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.0839

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.325

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.210

GnomAD4 exome

AF:

0.190

AC:

3271

AN:

17220

Hom.:

343

Cov.:

AF XY:

0.185

AC XY:

1735

AN XY:

9388

show subpopulations

African (AFR)

AF:

0.0733

AC:

AN:

150

American (AMR)

AF:

0.175

AC:

339

AN:

1938

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

AN:

220

East Asian (EAS)

AF:

0.0507

AC:

AN:

828

South Asian (SAS)

AF:

0.141

AC:

313

AN:

2222

European-Finnish (FIN)

AF:

0.228

AC:

106

AN:

464

Middle Eastern (MID)

AF:

0.429

AC:

AN:

European-Non Finnish (NFE)

AF:

0.211

AC:

2223

AN:

10560

Other (OTH)

AF:

0.216

AC:

172

AN:

796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

132

265

397

530

662

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.178

AC:

27046

AN:

152000

Hom.:

2907

Cov.:

AF XY:

0.176

AC XY:

13078

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.0666

AC:

2766

AN:

41508

American (AMR)

AF:

0.159

AC:

2419

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.293

AC:

1015

AN:

3468

East Asian (EAS)

AF:

0.0843

AC:

435

AN:

5162

South Asian (SAS)

AF:

0.133

AC:

642

AN:

4822

European-Finnish (FIN)

AF:

0.265

AC:

2793

AN:

10536

Middle Eastern (MID)

AF:

0.329

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.239

AC:

16218

AN:

67934

Other (OTH)

AF:

0.207

AC:

439

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1095

2189

3284

4378

5473

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

284

568

852

1136

1420

<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:

0.211

Hom.:

2256

Bravo

AF:

0.167

Asia WGS

AF:

0.107

AC:

372

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.041

(source)

DANN

Benign

0.46

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(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