chr1-33999854-T-C

Position:

• chr1-33999854-T-C

Variant summary

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

The NM_001281956.2(CSMD2):​c.517+32740A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0668 in 152,314 control chromosomes in the GnomAD database, including 422 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 0.067 (422 hom., cov: 32)
• Consequence: CSMD2 NM_001281956.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSMD2	NM_001281956.2	c.517+32740A>G		intron_variant		ENST00000373381.9	NP_001268885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSMD2	ENST00000373381.9	c.517+32740A>G		intron_variant		1	NM_001281956.2	ENSP00000362479	P2
CSMD2	ENST00000373388.7	c.397+32740A>G		intron_variant		1		ENSP00000362486
CSMD2	ENST00000619121.4	c.397+32740A>G		intron_variant		5		ENSP00000483463	A2

Frequencies

GnomAD3 genomes AF: 0.0669 AC: 10176 AN: 152196 Hom.: 421 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0497

Gnomad ASJ AF: 0.0854

Gnomad EAS AF: 0.00442

Gnomad SAS AF: 0.0362

Gnomad FIN AF: 0.0412

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0565

Gnomad OTH AF: 0.0750

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

GnomAD4 genome AF: 0.0668 AC: 10179 AN: 152314 Hom.: 422 Cov.: 32 AF XY: 0.0637 AC XY: 4746 AN XY: 74488

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0497

Gnomad4 ASJ AF: 0.0854

Gnomad4 EAS AF: 0.00463

Gnomad4 SAS AF: 0.0362

Gnomad4 FIN AF: 0.0412

Gnomad4 NFE AF: 0.0564

Gnomad4 OTH AF: 0.0738

Alfa AF: 0.0649 Hom.: 447

Bravo AF: 0.0714

Asia WGS AF: 0.0250 AC: 87 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.84

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: rs9425977; hg19: chr1-34465455;