rs13280616

Variant names:

• chr8-3033287-A-G
• rs13280616
• NM_033225.6:c.7661-3774T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033225.6(CSMD1):​c.7661-3774T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,038 control chromosomes in the GnomAD database, including 3,776 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 0.20 (3776 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.7661-3774T>C		intron_variant	Intron 50 of 69	ENST00000635120.2	NP_150094.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.7661-3774T>C		intron_variant	Intron 50 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29954 AN: 151920 Hom.: 3778 Cov.: 33

Gnomad AFR AF: 0.0837

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.217

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.197 AC: 29946 AN: 152038 Hom.: 3776 Cov.: 33 AF XY: 0.196 AC XY: 14540 AN XY: 74312

African (AFR) AF: 0.0835 AC: 3469 AN: 41532

American (AMR) AF: 0.197 AC: 3008 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 918 AN: 3456

East Asian (EAS) AF: 0.00250 AC: 13 AN: 5190

South Asian (SAS) AF: 0.105 AC: 505 AN: 4816

European-Finnish (FIN) AF: 0.262 AC: 2766 AN: 10572

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18595 AN: 67908

Other (OTH) AF: 0.214 AC: 451 AN: 2104

Alfa AF: 0.243 Hom.: 2258

Bravo AF: 0.190

Asia WGS AF: 0.0590 AC: 206 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	4.6
DANN	Benign	0.82
PhyloP100		0.066
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

Other links and lift over

dbSNP: rs13280616; hg19: chr8-2890809;