rs17630545

Variant names:

• chr8-112253640-T-C
• rs17630545
• NM_198123.2:c.10110+613A>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.10110+613A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 151,866 control chromosomes in the GnomAD database, including 3,001 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 0.18 (3001 hom., cov: 32)
• Consequence: CSMD3 NM_198123.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• Publications: 4 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=-0.51).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD3	NM_198123.2	c.10110+613A>G		intron_variant	Intron 63 of 70	ENST00000297405.10	NP_937756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD3	ENST00000297405.10	c.10110+613A>G		intron_variant	Intron 63 of 70	1	NM_198123.2	ENSP00000297405.5

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28059 AN: 151748 Hom.: 3002 Cov.: 32

Gnomad AFR AF: 0.0907

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.0833

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.185 AC: 28060 AN: 151866 Hom.: 3001 Cov.: 32 AF XY: 0.183 AC XY: 13592 AN XY: 74202

African (AFR) AF: 0.0907 AC: 3765 AN: 41514

American (AMR) AF: 0.160 AC: 2433 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1015 AN: 3470

East Asian (EAS) AF: 0.0837 AC: 433 AN: 5172

South Asian (SAS) AF: 0.133 AC: 641 AN: 4816

European-Finnish (FIN) AF: 0.265 AC: 2802 AN: 10560

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16206 AN: 67828

Other (OTH) AF: 0.211 AC: 444 AN: 2104

Alfa AF: 0.218 Hom.: 15052

Bravo AF: 0.175

Asia WGS AF: 0.109 AC: 381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	8.2
DANN	Benign	0.52
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs17630545; hg19: chr8-113265869;