rs643544

chr1-33705935-A-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+3154T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 144,986 control chromosomes in the GnomAD database, including 13,734 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 0.44 (13734 hom., cov: 29)
• Consequence: CSMD2 NM_001281956.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD2	NM_001281956.2	c.3576+3154T>A		intron_variant		ENST00000373381.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD2	ENST00000373381.9	c.3576+3154T>A		intron_variant		1	NM_001281956.2	P2
CSMD2	ENST00000373388.7	c.3456+3154T>A		intron_variant		1
CSMD2	ENST00000619121.4	c.3456+3154T>A		intron_variant		5		A2
CSMD2	ENST00000373380.5	n.416+3154T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.444 AC: 64265 AN: 144902 Hom.: 13719 Cov.: 29

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.444 AC: 64322 AN: 144986 Hom.: 13734 Cov.: 29 AF XY: 0.445 AC XY: 31375 AN XY: 70472

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.477

Alfa AF: 0.427 Hom.: 1457

Bravo AF: 0.432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.7
Dann	Benign	0.49

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: rs643544; hg19: chr1-34171535;