chr8-112370609-T-C

Variant names:

• chr8-112370609-T-C
• rs4556111
• NM_198123.2:c.6136+9743A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-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 rank	MANE	Protein	UniProt
CSMD3	NM_198123.2	c.6136+9743A>G		intron_variant	Intron 38 of 70	ENST00000297405.10	NP_937756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD3	ENST00000297405.10	c.6136+9743A>G		intron_variant	Intron 38 of 70	1	NM_198123.2	ENSP00000297405.5
CSMD3	ENST00000343508.7	c.6016+9743A>G		intron_variant	Intron 39 of 71	1		ENSP00000345799.3
CSMD3	ENST00000455883.2	c.5824+9743A>G		intron_variant	Intron 37 of 68	1		ENSP00000412263.2
CSMD3	ENST00000339701.7	c.3946+9743A>G		intron_variant	Intron 23 of 55	1		ENSP00000341558.3

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

African (AFR) AF: 0.800 AC: 33176 AN: 41468

American (AMR) AF: 0.574 AC: 8761 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2225 AN: 3470

East Asian (EAS) AF: 0.623 AC: 3206 AN: 5146

South Asian (SAS) AF: 0.510 AC: 2455 AN: 4816

European-Finnish (FIN) AF: 0.514 AC: 5418 AN: 10550

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36747 AN: 67950

Other (OTH) AF: 0.628 AC: 1327 AN: 2112

Alfa AF: 0.564 Hom.: 15657

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
PhyloP100		-1.2
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: rs4556111; hg19: chr8-113382838;