rs10505182

chr8-112255869-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198123.2(CSMD3):c.9863-442C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 169,220 control chromosomes in the GnomAD database, including 3,250 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 (2907 hom., cov: 32)
  • Exomes 𝑓: 0.19 (343 hom.)
• Consequence: CSMD3 NM_198123.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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/exons	MANE	UniProt
CSMD3	NM_198123.2	c.9863-442C>A		intron_variant		ENST00000297405.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD3	ENST00000297405.10	c.9863-442C>A		intron_variant		1	NM_198123.2	P1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27046 AN: 151880 Hom.: 2908 Cov.: 32

Gnomad AFR AF: 0.0667

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.0839

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.190 AC: 3271 AN: 17220 Hom.: 343 Cov.: 0 AF XY: 0.185 AC XY: 1735 AN XY: 9388

Gnomad4 AFR exome AF: 0.0733

Gnomad4 AMR exome AF: 0.175

Gnomad4 ASJ exome AF: 0.214

Gnomad4 EAS exome AF: 0.0507

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.228

Gnomad4 NFE exome AF: 0.211

Gnomad4 OTH exome AF: 0.216

GnomAD4 genome AF: 0.178 AC: 27046 AN: 152000 Hom.: 2907 Cov.: 32 AF XY: 0.176 AC XY: 13078 AN XY: 74264

Gnomad4 AFR AF: 0.0666

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.0843

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.207

Alfa AF: 0.211 Hom.: 1432

Bravo AF: 0.167

Asia WGS AF: 0.107 AC: 372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.041
Dann	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs10505182; hg19: chr8-113268098;