1-33778034-A-G

Variant names:

• chr1-33778034-A-G
• rs524787
• NM_001281956.2:c.1664-5283T>C

Variant summary

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

The NM_001281956.2(CSMD2):​c.1664-5283T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,030 control chromosomes in the GnomAD database, including 40,997 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 0.73 (40997 hom., cov: 31)
• Consequence: CSMD2 NM_001281956.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD2	NM_001281956.2	c.1664-5283T>C		intron_variant	Intron 12 of 70	ENST00000373381.9	NP_001268885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD2	ENST00000373381.9	c.1664-5283T>C		intron_variant	Intron 12 of 70	1	NM_001281956.2	ENSP00000362479.4
CSMD2	ENST00000373388.7	c.1544-5283T>C		intron_variant	Intron 12 of 69	1		ENSP00000362486.3
CSMD2	ENST00000338325.1	n.901-5283T>C		intron_variant	Intron 6 of 6	1
CSMD2	ENST00000619121.4	c.1544-5283T>C		intron_variant	Intron 12 of 70	5		ENSP00000483463.1

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110283 AN: 151912 Hom.: 40929 Cov.: 31

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.726 AC: 110413 AN: 152030 Hom.: 40997 Cov.: 31 AF XY: 0.726 AC XY: 53956 AN XY: 74320

African (AFR) AF: 0.875 AC: 36343 AN: 41516

American (AMR) AF: 0.754 AC: 11512 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 2329 AN: 3466

East Asian (EAS) AF: 0.815 AC: 4209 AN: 5164

South Asian (SAS) AF: 0.794 AC: 3819 AN: 4812

European-Finnish (FIN) AF: 0.602 AC: 6350 AN: 10542

Middle Eastern (MID) AF: 0.613 AC: 179 AN: 292

European-Non Finnish (NFE) AF: 0.643 AC: 43667 AN: 67952

Other (OTH) AF: 0.703 AC: 1480 AN: 2106

Alfa AF: 0.671 Hom.: 58452

Bravo AF: 0.741

Asia WGS AF: 0.794 AC: 2759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.5
DANN	Benign	0.63
PhyloP100		0.18
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: rs524787; hg19: chr1-34243635;