1-33829106-G-A

Variant names:

• chr1-33829106-G-A
• rs911213
• NM_001281956.2:c.1034-3332C>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.1034-3332C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,136 control chromosomes in the GnomAD database, including 47,771 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 (47771 hom., cov: 32)
• Consequence: CSMD2 NM_001281956.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.713
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD2	NM_001281956.2	c.1034-3332C>T		intron_variant	Intron 6 of 70	ENST00000373381.9	NP_001268885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD2	ENST00000373381.9	c.1034-3332C>T		intron_variant	Intron 6 of 70	1	NM_001281956.2	ENSP00000362479.4
CSMD2	ENST00000373388.7	c.914-3332C>T		intron_variant	Intron 6 of 69	1		ENSP00000362486.3
CSMD2	ENST00000619121.4	c.914-3332C>T		intron_variant	Intron 6 of 70	5		ENSP00000483463.1

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119382 AN: 152018 Hom.: 47719 Cov.: 32

Gnomad AFR AF: 0.919

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.901

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.848

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: 0.785 AC: 119494 AN: 152136 Hom.: 47771 Cov.: 32 AF XY: 0.790 AC XY: 58775 AN XY: 74354

African (AFR) AF: 0.919 AC: 38138 AN: 41510

American (AMR) AF: 0.835 AC: 12770 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2706 AN: 3468

East Asian (EAS) AF: 0.939 AC: 4857 AN: 5174

South Asian (SAS) AF: 0.900 AC: 4340 AN: 4820

European-Finnish (FIN) AF: 0.707 AC: 7479 AN: 10582

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.688 AC: 46755 AN: 67978

Other (OTH) AF: 0.776 AC: 1641 AN: 2114

Alfa AF: 0.724 Hom.: 31089

Bravo AF: 0.799

Asia WGS AF: 0.920 AC: 3201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.73
DANN	Benign	0.48
PhyloP100		-0.71
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: rs911213; hg19: chr1-34294707;