8-113010925-C-T

Position:

• chr8-113010925-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.1030+8142G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 151,286 control chromosomes in the GnomAD database, including 28,507 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 0.60 (28507 hom., cov: 31)
• Consequence: CSMD3 NM_198123.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSMD3	NM_198123.2	c.1030+8142G>A		intron_variant		ENST00000297405.10	NP_937756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSMD3	ENST00000297405.10	c.1030+8142G>A		intron_variant		1	NM_198123.2	ENSP00000297405.5
CSMD3	ENST00000343508.7	c.910+8142G>A		intron_variant		1		ENSP00000345799.3
CSMD3	ENST00000455883.2	c.1030+8142G>A		intron_variant		1		ENSP00000412263.2

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90397 AN: 151164 Hom.: 28470 Cov.: 31

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.504

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.598 AC: 90493 AN: 151286 Hom.: 28507 Cov.: 31 AF XY: 0.605 AC XY: 44744 AN XY: 73908

Gnomad4 AFR AF: 0.740

Gnomad4 AMR AF: 0.708

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.953

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.618

Alfa AF: 0.340 Hom.: 735

Bravo AF: 0.623

Asia WGS AF: 0.767 AC: 2623 AN: 3424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.25

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: rs1156075; hg19: chr8-114023154;