rs476463

Positions:

• chr1-33782463-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.1663+6137C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,054 control chromosomes in the GnomAD database, including 3,515 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 0.19 (3515 hom., cov: 31)
• Consequence: CSMD2 NM_001281956.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD2	NM_001281956.2	c.1663+6137C>T		intron_variant		ENST00000373381.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD2	ENST00000373381.9	c.1663+6137C>T		intron_variant		1	NM_001281956.2	P2
CSMD2	ENST00000373388.7	c.1543+6137C>T		intron_variant		1
CSMD2	ENST00000338325.1	n.900+6137C>T		intron_variant, non_coding_transcript_variant		1
CSMD2	ENST00000619121.4	c.1543+6137C>T		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28286 AN: 151936 Hom.: 3506 Cov.: 31

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0581

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.0894

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.186 AC: 28320 AN: 152054 Hom.: 3515 Cov.: 31 AF XY: 0.184 AC XY: 13706 AN XY: 74362

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.0579

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.0894

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.183

Alfa AF: 0.135 Hom.: 3379

Bravo AF: 0.192

Asia WGS AF: 0.145 AC: 502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.35
DANN	Benign	0.62

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: rs476463; hg19: chr1-34248064;