chr1-33782463-G-A

Variant names:

• chr1-33782463-G-A
• rs476463
• NM_001281956.2:c.1663+6137C>T

Variant summary

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

The NM_001281956.2(CSMD2):​c.1663+6137C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,054 control chromosomes in the GnomAD database, including 3,515 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 0.19 (3515 hom., cov: 31)
• Consequence: CSMD2 NM_001281956.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279
• Publications: 10 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.346 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.1663+6137C>T		intron	N/A	NP_001268885.1	Q7Z408-4
	CSMD2	NM_052896.5		c.1543+6137C>T		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.1663+6137C>T		intron	N/A	ENSP00000362479.4	Q7Z408-4
	CSMD2	ENST00000373388.7	TSL:1	c.1543+6137C>T		intron	N/A	ENSP00000362486.3	Q7Z408-1
	CSMD2	ENST00000338325.1	TSL:1	n.900+6137C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28286 AN: 151936 Hom.: 3506 Cov.: 31

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0581

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.0894

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.186 AC: 28320 AN: 152054 Hom.: 3515 Cov.: 31 AF XY: 0.184 AC XY: 13706 AN XY: 74362

African (AFR) AF: 0.351 AC: 14523 AN: 41410

American (AMR) AF: 0.134 AC: 2049 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 417 AN: 3472

East Asian (EAS) AF: 0.0579 AC: 300 AN: 5182

South Asian (SAS) AF: 0.224 AC: 1076 AN: 4810

European-Finnish (FIN) AF: 0.0894 AC: 947 AN: 10598

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.125 AC: 8504 AN: 67976

Other (OTH) AF: 0.183 AC: 386 AN: 2110

Alfa AF: 0.143 Hom.: 7804

Bravo AF: 0.192

Asia WGS AF: 0.145 AC: 502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.35
DANN	Benign	0.62
PhyloP100		-0.28
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: rs476463; hg19: chr1-34248064;