chr1-33517419-C-T

Variant names:

• chr1-33517419-C-T
• rs10798959
• NM_001281956.2:c.*54-849G>A

Variant summary

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

The NM_001281956.2(CSMD2):​c.*54-849G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,148 control chromosomes in the GnomAD database, including 6,118 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 0.28 (6118 hom., cov: 33)
• Consequence: CSMD2 NM_001281956.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• Publications: 5 publications found

Genes affected

CSMD2 (HGNC:19290): (CUB and Sushi multiple domains 2) The protein encoded by this gene is thought to be involved in the control of complement cascade of the immune system. Defects in this gene have been associated with schizophrenia. This gene may act as a tumor suppressor for colorectal cancer. [provided by RefSeq, Jan 2020]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001281956.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD2	NM_001281956.2	MANE Select	c.*54-849G>A		intron	N/A	NP_001268885.1	Q7Z408-4
	CSMD2	NM_052896.5		c.*54-849G>A		intron	N/A	NP_443128.2	Q7Z408-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD2	ENST00000373381.9	TSL:1 MANE Select	c.*54-849G>A		intron	N/A	ENSP00000362479.4	Q7Z408-4
	CSMD2	ENST00000373388.7	TSL:1	c.*54-849G>A		intron	N/A	ENSP00000362486.3	Q7Z408-1
	CSMD2	ENST00000619121.4	TSL:5	c.*54-849G>A		intron	N/A	ENSP00000483463.1	A0A087X0K4

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42531 AN: 152030 Hom.: 6116 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.280 AC: 42557 AN: 152148 Hom.: 6118 Cov.: 33 AF XY: 0.279 AC XY: 20764 AN XY: 74378

African (AFR) AF: 0.226 AC: 9367 AN: 41500

American (AMR) AF: 0.249 AC: 3809 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 680 AN: 3468

East Asian (EAS) AF: 0.399 AC: 2060 AN: 5164

South Asian (SAS) AF: 0.368 AC: 1774 AN: 4820

European-Finnish (FIN) AF: 0.267 AC: 2826 AN: 10588

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21002 AN: 67994

Other (OTH) AF: 0.278 AC: 587 AN: 2112

Alfa AF: 0.284 Hom.: 12163

Bravo AF: 0.273

Asia WGS AF: 0.360 AC: 1251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.021
DANN	Benign	0.67
PhyloP100		-1.8
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: rs10798959; hg19: chr1-33983019; COSMIC: COSV53892389; COSMIC: COSV53892389;