1-33517419-C-T

Position:

• chr1-33517419-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSMD2	NM_001281956.2	c.*54-849G>A		intron_variant		ENST00000373381.9	NP_001268885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSMD2	ENST00000373381.9	c.*54-849G>A		intron_variant		1	NM_001281956.2	ENSP00000362479.4
CSMD2	ENST00000373388.7	c.*54-849G>A		intron_variant		1		ENSP00000362486.3
CSMD2	ENST00000619121.4	c.*54-849G>A		intron_variant		5		ENSP00000483463.1

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

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.278

Alfa AF: 0.288 Hom.: 8653

Bravo AF: 0.273

Asia WGS AF: 0.360 AC: 1251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.021
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs10798959; hg19: chr1-33983019; COSMIC: COSV53892389; COSMIC: COSV53892389;