Genetic Variant NM_033225.6:c.6430+140C>T (chr8-3118259-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_033225.6(CSMD1):c.6430+140C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 642,442 control chromosomes in the GnomAD database, including 20,780 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 0.30 ( 11842 hom., cov: 33)

Exomes 𝑓: 0.15 ( 8938 hom. )

Consequence

CSMD1
NM_033225.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.34

Publications

3 publications found

Variant links:

Genes affected

CSMD1 (HGNC:14026): (CUB and Sushi multiple domains 1) Predicted to act upstream of or within several processes, including learning or memory; mammary gland branching involved in pregnancy; and reproductive structure development. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CSMD1 Gene-Disease associations (from GenCC):

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

CSMD1 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=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6 link	c.6430+140C>T		intron_variant	Intron 42 of 69	ENST00000635120.2	NP_150094.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2 link	c.6430+140C>T		intron_variant	Intron 42 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes

AF:

0.296

AC:

44940

AN:

151996

Hom.:

11816

Cov.:

show subpopulations

Gnomad AFR

AF:

0.705

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.379

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.152

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.252

GnomAD4 exome

AF:

0.153

AC:

75185

AN:

490328

Hom.:

8938

AF XY:

0.151

AC XY:

38490

AN XY:

255542

show subpopulations

African (AFR)

AF:

0.705

AC:

8733

AN:

12396

American (AMR)

AF:

0.132

AC:

2169

AN:

16380

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

2092

AN:

13600

East Asian (EAS)

AF:

0.382

AC:

11473

AN:

29998

South Asian (SAS)

AF:

0.140

AC:

5855

AN:

41768

European-Finnish (FIN)

AF:

0.139

AC:

4246

AN:

30590

Middle Eastern (MID)

AF:

0.193

AC:

394

AN:

2040

European-Non Finnish (NFE)

AF:

0.112

AC:

35525

AN:

316458

Other (OTH)

AF:

0.173

AC:

4698

AN:

27098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

2750

5500

8251

11001

13751

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

546

1092

1638

2184

2730

<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:

0.296

AC:

45014

AN:

152114

Hom.:

11842

Cov.:

AF XY:

0.292

AC XY:

21710

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.705

AC:

29266

AN:

41522

American (AMR)

AF:

0.157

AC:

2405

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.148

AC:

513

AN:

3464

East Asian (EAS)

AF:

0.379

AC:

1963

AN:

5176

South Asian (SAS)

AF:

0.146

AC:

703

AN:

4816

European-Finnish (FIN)

AF:

0.152

AC:

1605

AN:

10564

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.115

AC:

7831

AN:

67980

Other (OTH)

AF:

0.251

AC:

532

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1123

2246

3369

4492

5615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.176

Hom.:

14258

Bravo

AF:

0.316

Asia WGS

AF:

0.234

AC:

814

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.21

(source)

DANN

Benign

0.75

PhyloP100

-1.3

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