8-112506238-C-T

Position:

• chr8-112506238-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD3	NM_198123.2	c.4895+453G>A		intron_variant		ENST00000297405.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD3	ENST00000297405.10	c.4895+453G>A		intron_variant		1	NM_198123.2	P1
CSMD3	ENST00000339701.7	c.2915+453G>A		intron_variant		1
CSMD3	ENST00000343508.7	c.4775+453G>A		intron_variant		1
CSMD3	ENST00000455883.2	c.4583+453G>A		intron_variant		1

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

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.273

Alfa AF: 0.243 Hom.: 5130

Bravo AF: 0.277

Asia WGS AF: 0.321 AC: 1114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.38
DANN	Benign	0.36

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: rs896760; hg19: chr8-113518467;