Genetic Variant NM_033225.6:c.6836-521G>A (chr8-3107162-C-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_033225.6(CSMD1):c.6836-521G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 155,370 control chromosomes in the GnomAD database, including 64,688 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 0.91 ( 63271 hom., cov: 32)

Exomes 𝑓: 0.95 ( 1417 hom. )

Consequence

CSMD1
NM_033225.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.79

Publications

2 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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6 link	c.6836-521G>A		intron_variant	Intron 45 of 69	ENST00000635120.2	NP_150094.5	Q96PZ7-1Q59FF8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2 link	c.6836-521G>A		intron_variant	Intron 45 of 69	5	NM_033225.6	ENSP00000489225.1		Q96PZ7-1

Frequencies

GnomAD3 genomes

AF:

0.907

AC:

138002

AN:

152102

Hom.:

63240

Cov.:

show subpopulations

Gnomad AFR

AF:

0.764

Gnomad AMI

AF:

0.957

Gnomad AMR

AF:

0.950

Gnomad ASJ

AF:

0.950

Gnomad EAS

AF:

0.957

Gnomad SAS

AF:

0.947

Gnomad FIN

AF:

0.982

Gnomad MID

AF:

0.943

Gnomad NFE

AF:

0.963

Gnomad OTH

AF:

0.921

GnomAD4 exome

AF:

0.947

AC:

2983

AN:

3150

Hom.:

1417

Cov.:

AF XY:

0.943

AC XY:

1576

AN XY:

1672

show subpopulations

African (AFR)

AF:

0.714

AC:

AN:

American (AMR)

AF:

0.948

AC:

237

AN:

250

Ashkenazi Jewish (ASJ)

AF:

0.947

AC:

AN:

East Asian (EAS)

AF:

0.976

AC:

AN:

South Asian (SAS)

AF:

0.900

AC:

162

AN:

180

European-Finnish (FIN)

AF:

0.988

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.954

AC:

2235

AN:

2342

Other (OTH)

AF:

0.903

AC:

159

AN:

176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.907

AC:

138082

AN:

152220

Hom.:

63271

Cov.:

AF XY:

0.911

AC XY:

67812

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.764

AC:

31674

AN:

41458

American (AMR)

AF:

0.950

AC:

14540

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.950

AC:

3297

AN:

3470

East Asian (EAS)

AF:

0.957

AC:

4964

AN:

5186

South Asian (SAS)

AF:

0.948

AC:

4575

AN:

4826

European-Finnish (FIN)

AF:

0.982

AC:

10431

AN:

10624

Middle Eastern (MID)

AF:

0.949

AC:

279

AN:

294

European-Non Finnish (NFE)

AF:

0.963

AC:

65504

AN:

68036

Other (OTH)

AF:

0.920

AC:

1947

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

598

1195

1793

2390

2988

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

902

1804

2706

3608

4510

<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:

0.945

Hom.:

9017

Bravo

AF:

0.900

Asia WGS

AF:

0.920

AC:

3200

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.035

(source)

DANN

Benign

0.16

PhyloP100

-2.8

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