8-112908212-T-C

Position:

• chr8-112908212-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.1633+13415A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.859 in 151,262 control chromosomes in the GnomAD database, including 56,099 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 0.86 (56099 hom., cov: 31)
• Consequence: CSMD3 NM_198123.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSMD3	NM_198123.2	c.1633+13415A>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.1633+13415A>G		intron_variant		1	NM_198123.2	ENSP00000297405.5
CSMD3	ENST00000343508.7	c.1513+13415A>G		intron_variant		1		ENSP00000345799.3
CSMD3	ENST00000455883.2	c.1321+13415A>G		intron_variant		1		ENSP00000412263.2

Frequencies

GnomAD3 genomes AF: 0.859 AC: 129773 AN: 151144 Hom.: 56044 Cov.: 31

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.863

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

GnomAD4 genome AF: 0.859 AC: 129890 AN: 151262 Hom.: 56099 Cov.: 31 AF XY: 0.862 AC XY: 63658 AN XY: 73854

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.884

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.931

Gnomad4 SAS AF: 0.815

Gnomad4 FIN AF: 0.851

Gnomad4 NFE AF: 0.807

Gnomad4 OTH AF: 0.861

Alfa AF: 0.848 Hom.: 8657

Bravo AF: 0.866

Asia WGS AF: 0.866 AC: 2987 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.8
DANN	Benign	0.69

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: rs4876501; hg19: chr8-113920441;