8-112370609-T-C

Variant summary

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

The NM_198123.2(CSMD3):c.6136+9743A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 151,970 control chromosomes in the GnomAD database, including 30,313 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 0.62 (30313 hom., cov: 31)
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD3	NM_198123.2	c.6136+9743A>G		intron_variant		ENST00000297405.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD3	ENST00000297405.10	c.6136+9743A>G		intron_variant		1	NM_198123.2	P1
CSMD3	ENST00000339701.7	c.3946+9743A>G		intron_variant		1
CSMD3	ENST00000343508.7	c.6016+9743A>G		intron_variant		1
CSMD3	ENST00000455883.2	c.5824+9743A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.619 AC: 93977 AN: 151852 Hom.: 30280 Cov.: 31

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.619 AC: 94060 AN: 151970 Hom.: 30313 Cov.: 31 AF XY: 0.613 AC XY: 45558 AN XY: 74274

Gnomad4 AFR AF: 0.800

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.641

Gnomad4 EAS AF: 0.623

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.628

Alfa AF: 0.565 Hom.: 14450

Bravo AF: 0.632

Asia WGS AF: 0.591 AC: 2056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.41
Dann	Benign	0.41

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: rs4556111; hg19: chr8-113382838;