chr1-33958792-T-C

Variant names:

• chr1-33958792-T-C
• rs549048
• NM_001281956.2:c.518-22838A>G

Variant summary

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

The NM_001281956.2(CSMD2):​c.518-22838A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 152,032 control chromosomes in the GnomAD database, including 25,627 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 0.57 (25627 hom., cov: 32)
• Consequence: CSMD2 NM_001281956.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD2	NM_001281956.2	c.518-22838A>G		intron_variant	Intron 3 of 70	ENST00000373381.9	NP_001268885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD2	ENST00000373381.9	c.518-22838A>G		intron_variant	Intron 3 of 70	1	NM_001281956.2	ENSP00000362479.4
CSMD2	ENST00000373388.7	c.398-22838A>G		intron_variant	Intron 3 of 69	1		ENSP00000362486.3
CSMD2	ENST00000619121.4	c.398-22838A>G		intron_variant	Intron 3 of 70	5		ENSP00000483463.1

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87113 AN: 151914 Hom.: 25588 Cov.: 32

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.574 AC: 87200 AN: 152032 Hom.: 25627 Cov.: 32 AF XY: 0.566 AC XY: 42032 AN XY: 74292

Gnomad4 AFR AF: 0.707

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.567

Alfa AF: 0.541 Hom.: 34004

Bravo AF: 0.574

Asia WGS AF: 0.491 AC: 1706 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	0.23
DANN	Benign	0.35

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: rs549048; hg19: chr1-34424393;