1-33708220-C-T

Variant names:

• chr1-33708220-C-T
• rs564148
• NM_001281956.2:c.3576+869G>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.3576+869G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.898 in 152,204 control chromosomes in the GnomAD database, including 61,610 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 0.90 (61610 hom., cov: 31)
• Consequence: CSMD2 NM_001281956.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.902
• Publications: 6 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]

ENSG00000297811 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.956 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.3576+869G>A		intron	N/A	NP_001268885.1
	CSMD2	NM_052896.5		c.3456+869G>A		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.3576+869G>A		intron	N/A	ENSP00000362479.4
	CSMD2	ENST00000373388.7	TSL:1	c.3456+869G>A		intron	N/A	ENSP00000362486.3
	CSMD2	ENST00000619121.4	TSL:5	c.3456+869G>A		intron	N/A	ENSP00000483463.1

Frequencies

GnomAD3 genomes AF: 0.898 AC: 136618 AN: 152086 Hom.: 61552 Cov.: 31

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.911

Gnomad ASJ AF: 0.921

Gnomad EAS AF: 0.903

Gnomad SAS AF: 0.894

Gnomad FIN AF: 0.914

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.907

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

GnomAD4 genome AF: 0.898 AC: 136736 AN: 152204 Hom.: 61610 Cov.: 31 AF XY: 0.902 AC XY: 67085 AN XY: 74404

African (AFR) AF: 0.964 AC: 40058 AN: 41538

American (AMR) AF: 0.912 AC: 13942 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.921 AC: 3198 AN: 3472

East Asian (EAS) AF: 0.903 AC: 4678 AN: 5182

South Asian (SAS) AF: 0.894 AC: 4313 AN: 4822

European-Finnish (FIN) AF: 0.914 AC: 9674 AN: 10590

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.851 AC: 57891 AN: 67996

Other (OTH) AF: 0.909 AC: 1913 AN: 2104

Alfa AF: 0.875 Hom.: 99477

Bravo AF: 0.901

Asia WGS AF: 0.897 AC: 3119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.71
DANN	Benign	0.65
PhyloP100		-0.90
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: rs564148; hg19: chr1-34173820;