8-112735587-C-T

Variant names:

• chr8-112735587-C-T
• rs1019603
• NM_198123.2:c.1973-45537G>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.1973-45537G>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 151,792 control chromosomes in the GnomAD database, including 9,272 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 (9272 hom., cov: 32)
• Consequence: CSMD3 NM_198123.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD3	NM_198123.2	c.1973-45537G>A		intron_variant	Intron 13 of 70	ENST00000297405.10	NP_937756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD3	ENST00000297405.10	c.1973-45537G>A		intron_variant	Intron 13 of 70	1	NM_198123.2	ENSP00000297405.5
CSMD3	ENST00000343508.7	c.1853-45537G>A		intron_variant	Intron 14 of 71	1		ENSP00000345799.3
CSMD3	ENST00000455883.2	c.1661-45537G>A		intron_variant	Intron 12 of 68	1		ENSP00000412263.2

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50475 AN: 151674 Hom.: 9265 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.333 AC: 50512 AN: 151792 Hom.: 9272 Cov.: 32 AF XY: 0.336 AC XY: 24917 AN XY: 74170

African (AFR) AF: 0.498 AC: 20609 AN: 41408

American (AMR) AF: 0.299 AC: 4550 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 871 AN: 3460

East Asian (EAS) AF: 0.366 AC: 1883 AN: 5140

South Asian (SAS) AF: 0.279 AC: 1343 AN: 4816

European-Finnish (FIN) AF: 0.307 AC: 3239 AN: 10556

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17157 AN: 67906

Other (OTH) AF: 0.298 AC: 628 AN: 2108

Alfa AF: 0.305 Hom.: 1310

Bravo AF: 0.339

Asia WGS AF: 0.318 AC: 1104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.39
PhyloP100		-1.4
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: rs1019603; hg19: chr8-113747816;