8-113227258-T-C

Position:

• chr8-113227258-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.514+51334A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 151,426 control chromosomes in the GnomAD database, including 36,449 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 0.68 (36449 hom., cov: 31)
• Consequence: CSMD3 NM_198123.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD3	NM_198123.2	c.514+51334A>G		intron_variant		ENST00000297405.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD3	ENST00000297405.10	c.514+51334A>G		intron_variant		1	NM_198123.2	P1
CSMD3	ENST00000343508.7	c.394+51334A>G		intron_variant		1
CSMD3	ENST00000455883.2	c.514+51334A>G		intron_variant		1
CSMD3	ENST00000497026.5	n.599+51334A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102107 AN: 151308 Hom.: 36388 Cov.: 31

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.675 AC: 102235 AN: 151426 Hom.: 36449 Cov.: 31 AF XY: 0.682 AC XY: 50458 AN XY: 73960

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.955

Gnomad4 SAS AF: 0.710

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.688

Alfa AF: 0.635 Hom.: 5301

Bravo AF: 0.700

Asia WGS AF: 0.814 AC: 2829 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.052
DANN	Benign	0.42

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: rs2356203; hg19: chr8-114239487;