1-33708220-C-T

Position:

• chr1-33708220-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.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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSMD2	NM_001281956.2	c.3576+869G>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.3576+869G>A		intron_variant		1	NM_001281956.2	ENSP00000362479	P2
CSMD2	ENST00000373388.7	c.3456+869G>A		intron_variant		1		ENSP00000362486
CSMD2	ENST00000619121.4	c.3456+869G>A		intron_variant		5		ENSP00000483463	A2
CSMD2	ENST00000373380.5	n.416+869G>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.964

Gnomad4 AMR AF: 0.912

Gnomad4 ASJ AF: 0.921

Gnomad4 EAS AF: 0.903

Gnomad4 SAS AF: 0.894

Gnomad4 FIN AF: 0.914

Gnomad4 NFE AF: 0.851

Gnomad4 OTH AF: 0.909

Alfa AF: 0.891 Hom.: 13442

Bravo AF: 0.901

Asia WGS AF: 0.897 AC: 3119 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	0.71
DANN	Benign	0.65

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: rs564148; hg19: chr1-34173820;