1-33576185-G-A

Position:

• chr1-33576185-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001281956.2(CSMD2):​c.7576+1111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,174 control chromosomes in the GnomAD database, including 1,416 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 0.12 (1416 hom., cov: 32)
• Consequence: CSMD2 NM_001281956.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSMD2	NM_001281956.2	c.7576+1111C>T		intron_variant		ENST00000373381.9	NP_001268885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSMD2	ENST00000373381.9	c.7576+1111C>T		intron_variant		1	NM_001281956.2	ENSP00000362479	P2
CSMD2	ENST00000373388.7	c.7582+1111C>T		intron_variant		1		ENSP00000362486
CSMD2	ENST00000619121.4	c.7456+1111C>T		intron_variant		5		ENSP00000483463	A2

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18574 AN: 152056 Hom.: 1417 Cov.: 32

Gnomad AFR AF: 0.0334

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0890

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.122 AC: 18569 AN: 152174 Hom.: 1416 Cov.: 32 AF XY: 0.119 AC XY: 8835 AN XY: 74378

Gnomad4 AFR AF: 0.0333

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0890

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.123

Alfa AF: 0.130 Hom.: 250

Bravo AF: 0.117

Asia WGS AF: 0.167 AC: 584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	10
DANN	Benign	0.70

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: rs16835611; hg19: chr1-34041785;