NM_033225.6:c.302+93740T>C

Variant names:

• chr8-4543602-A-G
• rs11786902
• NM_033225.6:c.302+93740T>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.302+93740T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 149,426 control chromosomes in the GnomAD database, including 6,793 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 0.29 (6793 hom., cov: 26)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033225.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	NM_033225.6	MANE Select	c.302+93740T>C		intron	N/A	NP_150094.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	ENST00000635120.2	TSL:5 MANE Select	c.302+93740T>C		intron	N/A	ENSP00000489225.1
	CSMD1	ENST00000520002.5	TSL:5	c.302+93740T>C		intron	N/A	ENSP00000430733.1
	CSMD1	ENST00000602557.5	TSL:5	c.302+93740T>C		intron	N/A	ENSP00000473359.1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 42642 AN: 149312 Hom.: 6791 Cov.: 26

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.340

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.285 AC: 42644 AN: 149426 Hom.: 6793 Cov.: 26 AF XY: 0.286 AC XY: 20793 AN XY: 72708

African (AFR) AF: 0.167 AC: 6774 AN: 40604

American (AMR) AF: 0.241 AC: 3598 AN: 14918

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1385 AN: 3464

East Asian (EAS) AF: 0.395 AC: 1977 AN: 5010

South Asian (SAS) AF: 0.388 AC: 1825 AN: 4702

European-Finnish (FIN) AF: 0.305 AC: 3026 AN: 9934

Middle Eastern (MID) AF: 0.336 AC: 98 AN: 292

European-Non Finnish (NFE) AF: 0.339 AC: 22925 AN: 67550

Other (OTH) AF: 0.310 AC: 633 AN: 2044

Alfa AF: 0.329 Hom.: 37194

Bravo AF: 0.277

Asia WGS AF: 0.351 AC: 1220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.090
DANN	Benign	0.44
PhyloP100		-1.5
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: rs11786902; hg19: chr8-4401124;