1-33828700-T-C

Variant names:

• chr1-33828700-T-C
• rs1570092
• NM_001281956.2:c.1034-2926A>G

Variant summary

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

The NM_001281956.2(CSMD2):​c.1034-2926A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 152,070 control chromosomes in the GnomAD database, including 47,786 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 0.79 (47786 hom., cov: 30)
• Consequence: CSMD2 NM_001281956.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 4 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=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.916 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD2	NM_001281956.2	MANE Select	c.1034-2926A>G		intron	N/A	NP_001268885.1
	CSMD2	NM_052896.5		c.914-2926A>G		intron	N/A	NP_443128.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD2	ENST00000373381.9	TSL:1 MANE Select	c.1034-2926A>G		intron	N/A	ENSP00000362479.4
	CSMD2	ENST00000373388.7	TSL:1	c.914-2926A>G		intron	N/A	ENSP00000362486.3
	CSMD2	ENST00000619121.4	TSL:5	c.914-2926A>G		intron	N/A	ENSP00000483463.1

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119366 AN: 151952 Hom.: 47735 Cov.: 30

Gnomad AFR AF: 0.920

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.847

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.786 AC: 119477 AN: 152070 Hom.: 47786 Cov.: 30 AF XY: 0.791 AC XY: 58760 AN XY: 74326

African (AFR) AF: 0.920 AC: 38168 AN: 41496

American (AMR) AF: 0.835 AC: 12775 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2707 AN: 3470

East Asian (EAS) AF: 0.939 AC: 4830 AN: 5146

South Asian (SAS) AF: 0.900 AC: 4338 AN: 4822

European-Finnish (FIN) AF: 0.706 AC: 7460 AN: 10564

Middle Eastern (MID) AF: 0.842 AC: 246 AN: 292

European-Non Finnish (NFE) AF: 0.688 AC: 46756 AN: 67966

Other (OTH) AF: 0.776 AC: 1639 AN: 2112

Alfa AF: 0.747 Hom.: 18637

Bravo AF: 0.799

Asia WGS AF: 0.920 AC: 3201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	3.8
DANN	Benign	0.78
PhyloP100		-1.3
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: rs1570092; hg19: chr1-34294301;