chr8-4420468-C-T

Variant summary

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

The NM_033225.6(CSMD1):​c.303-403G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 151,868 control chromosomes in the GnomAD database, including 8,031 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 ( 8031 hom., cov: 32)

Consequence

CSMD1
NM_033225.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.159

Publications

5 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

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=-1.0).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CSMD1NM_033225.6 linkc.303-403G>A intron_variant Intron 2 of 69 ENST00000635120.2 NP_150094.5 Q96PZ7-1Q59FF8
CSMD1XM_011534752.3 linkc.303-403G>A intron_variant Intron 2 of 68 XP_011533054.1
CSMD1XM_017013731.2 linkc.303-403G>A intron_variant Intron 2 of 63 XP_016869220.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CSMD1ENST00000635120.2 linkc.303-403G>A intron_variant Intron 2 of 69 5 NM_033225.6 ENSP00000489225.1 Q96PZ7-1

Frequencies

GnomAD3 genomes
AF:
0.296
AC:
44915
AN:
151750
Hom.:
8028
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0990
Gnomad AMI
AF:
0.284
Gnomad AMR
AF:
0.319
Gnomad ASJ
AF:
0.454
Gnomad EAS
AF:
0.207
Gnomad SAS
AF:
0.312
Gnomad FIN
AF:
0.304
Gnomad MID
AF:
0.326
Gnomad NFE
AF:
0.406
Gnomad OTH
AF:
0.340
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.296
AC:
44926
AN:
151868
Hom.:
8031
Cov.:
32
AF XY:
0.292
AC XY:
21633
AN XY:
74200
show subpopulations
African (AFR)
AF:
0.0987
AC:
4092
AN:
41458
American (AMR)
AF:
0.318
AC:
4851
AN:
15236
Ashkenazi Jewish (ASJ)
AF:
0.454
AC:
1574
AN:
3468
East Asian (EAS)
AF:
0.208
AC:
1068
AN:
5138
South Asian (SAS)
AF:
0.314
AC:
1515
AN:
4824
European-Finnish (FIN)
AF:
0.304
AC:
3196
AN:
10530
Middle Eastern (MID)
AF:
0.316
AC:
93
AN:
294
European-Non Finnish (NFE)
AF:
0.406
AC:
27556
AN:
67904
Other (OTH)
AF:
0.343
AC:
723
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1473
2946
4419
5892
7365
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
456
912
1368
1824
2280
<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.:
520
Bravo
AF:
0.284

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.54
DANN
Benign
0.46
PhyloP100
-0.16
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12681349; hg19: chr8-4277990; API