8-112908212-T-C

Variant names:

• chr8-112908212-T-C
• rs4876501
• NM_198123.2:c.1633+13415A>G

Variant summary

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

The NM_198123.2(CSMD3):​c.1633+13415A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.859 in 151,262 control chromosomes in the GnomAD database, including 56,099 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 0.86 (56099 hom., cov: 31)
• Consequence: CSMD3 NM_198123.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107
• Publications: 1 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.933 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD3	NM_198123.2	MANE Select	c.1633+13415A>G		intron	N/A	NP_937756.1
	CSMD3	NM_198124.2		c.1513+13415A>G		intron	N/A	NP_937757.1
	CSMD3	NM_052900.3		c.1321+13415A>G		intron	N/A	NP_443132.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD3	ENST00000297405.10	TSL:1 MANE Select	c.1633+13415A>G		intron	N/A	ENSP00000297405.5
	CSMD3	ENST00000343508.7	TSL:1	c.1513+13415A>G		intron	N/A	ENSP00000345799.3
	CSMD3	ENST00000455883.2	TSL:1	c.1321+13415A>G		intron	N/A	ENSP00000412263.2

Frequencies

GnomAD3 genomes AF: 0.859 AC: 129773 AN: 151144 Hom.: 56044 Cov.: 31

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.863

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

GnomAD4 genome AF: 0.859 AC: 129890 AN: 151262 Hom.: 56099 Cov.: 31 AF XY: 0.862 AC XY: 63658 AN XY: 73854

African (AFR) AF: 0.940 AC: 38981 AN: 41448

American (AMR) AF: 0.884 AC: 13336 AN: 15088

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2634 AN: 3458

East Asian (EAS) AF: 0.931 AC: 4756 AN: 5110

South Asian (SAS) AF: 0.815 AC: 3925 AN: 4814

European-Finnish (FIN) AF: 0.851 AC: 8999 AN: 10578

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.807 AC: 54451 AN: 67464

Other (OTH) AF: 0.861 AC: 1805 AN: 2096

Alfa AF: 0.848 Hom.: 8657

Bravo AF: 0.866

Asia WGS AF: 0.866 AC: 2987 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.8
DANN	Benign	0.69
PhyloP100		-0.11
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: rs4876501; hg19: chr8-113920441;