8-112506238-C-T

Variant names:

• chr8-112506238-C-T
• rs896760
• NM_198123.2:c.4895+453G>A

Variant summary

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

The NM_198123.2(CSMD3):​c.4895+453G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 151,816 control chromosomes in the GnomAD database, including 5,513 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 0.26 (5513 hom., cov: 33)
• Consequence: CSMD3 NM_198123.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316
• Publications: 2 publications found

Genes affected

CSMD3 (HGNC:19291): (CUB and Sushi multiple domains 3) Predicted to be involved in regulation of dendrite development. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CSMD3 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198123.2. 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
	CSMD3	NM_198123.2	MANE Select	c.4895+453G>A		intron	N/A	NP_937756.1
	CSMD3	NM_198124.2		c.4775+453G>A		intron	N/A	NP_937757.1
	CSMD3	NM_052900.3		c.4583+453G>A		intron	N/A	NP_443132.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD3	ENST00000297405.10	TSL:1 MANE Select	c.4895+453G>A		intron	N/A	ENSP00000297405.5
	CSMD3	ENST00000343508.7	TSL:1	c.4775+453G>A		intron	N/A	ENSP00000345799.3
	CSMD3	ENST00000455883.2	TSL:1	c.4583+453G>A		intron	N/A	ENSP00000412263.2

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39883 AN: 151696 Hom.: 5505 Cov.: 33

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.263 AC: 39917 AN: 151816 Hom.: 5513 Cov.: 33 AF XY: 0.263 AC XY: 19509 AN XY: 74164

African (AFR) AF: 0.265 AC: 10964 AN: 41408

American (AMR) AF: 0.315 AC: 4795 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1041 AN: 3464

East Asian (EAS) AF: 0.475 AC: 2455 AN: 5170

South Asian (SAS) AF: 0.272 AC: 1310 AN: 4812

European-Finnish (FIN) AF: 0.193 AC: 2038 AN: 10534

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16335 AN: 67876

Other (OTH) AF: 0.273 AC: 577 AN: 2110

Alfa AF: 0.246 Hom.: 6175

Bravo AF: 0.277

Asia WGS AF: 0.321 AC: 1114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.38
DANN	Benign	0.36
PhyloP100		-0.32
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: rs896760; hg19: chr8-113518467;