rs10505196

Positions:

• chr8-112949729-A-C

Variant summary

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

The NM_198123.2(CSMD3):​c.1421-1852T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,864 control chromosomes in the GnomAD database, including 14,672 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 0.43 (14672 hom., cov: 32)
• Consequence: CSMD3 NM_198123.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.863

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSMD3	NM_198123.2	c.1421-1852T>G		intron_variant		ENST00000297405.10	NP_937756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSMD3	ENST00000297405.10	c.1421-1852T>G		intron_variant		1	NM_198123.2	ENSP00000297405	P1
CSMD3	ENST00000343508.7	c.1301-1852T>G		intron_variant		1		ENSP00000345799
CSMD3	ENST00000455883.2	c.1109-1852T>G		intron_variant		1		ENSP00000412263

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64839 AN: 151746 Hom.: 14665 Cov.: 32

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.427 AC: 64883 AN: 151864 Hom.: 14672 Cov.: 32 AF XY: 0.436 AC XY: 32342 AN XY: 74232

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.618

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.472

Alfa AF: 0.419 Hom.: 22035

Bravo AF: 0.447

Asia WGS AF: 0.570 AC: 1981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.6
DANN	Benign	0.51

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: rs10505196; hg19: chr8-113961958;