8-113099988-C-T

Variant names:

• chr8-113099988-C-T
• rs9332440
• NM_198123.2:c.710-1025G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198123.2(CSMD3):​c.710-1025G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,796 control chromosomes in the GnomAD database, including 9,223 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 0.33 (9223 hom., cov: 32)
• Consequence: CSMD3 NM_198123.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.390
• Publications: 0 publications found

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]

CSMD3 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD3	NM_198123.2	c.710-1025G>A		intron_variant	Intron 4 of 70	ENST00000297405.10	NP_937756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD3	ENST00000297405.10	c.710-1025G>A		intron_variant	Intron 4 of 70	1	NM_198123.2	ENSP00000297405.5

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50457 AN: 151676 Hom.: 9214 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.333 AC: 50495 AN: 151796 Hom.: 9223 Cov.: 32 AF XY: 0.340 AC XY: 25234 AN XY: 74178

African (AFR) AF: 0.337 AC: 13933 AN: 41376

American (AMR) AF: 0.516 AC: 7862 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 962 AN: 3468

East Asian (EAS) AF: 0.686 AC: 3545 AN: 5170

South Asian (SAS) AF: 0.368 AC: 1774 AN: 4826

European-Finnish (FIN) AF: 0.297 AC: 3123 AN: 10524

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18179 AN: 67892

Other (OTH) AF: 0.347 AC: 731 AN: 2106

Alfa AF: 0.295 Hom.: 847

Bravo AF: 0.355

Asia WGS AF: 0.470 AC: 1630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.0
DANN	Benign	0.58
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9332440; hg19: chr8-114112217;