rs2449222

Variant names:

• chr8-3625889-T-C
• rs2449222
• NM_033225.6:c.1010-9092A>G

Variant summary

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

The NM_033225.6(CSMD1):​c.1010-9092A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,164 control chromosomes in the GnomAD database, including 1,277 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 0.11 (1277 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.476
• Publications: 3 publications found

Genes affected

CSMD1 (HGNC:14026): (CUB and Sushi multiple domains 1) Predicted to act upstream of or within several processes, including learning or memory; mammary gland branching involved in pregnancy; and reproductive structure development. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CSMD1 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000307692 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033225.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	NM_033225.6	MANE Select	c.1010-9092A>G		intron	N/A	NP_150094.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	ENST00000635120.2	TSL:5 MANE Select	c.1010-9092A>G		intron	N/A	ENSP00000489225.1	Q96PZ7-1
	CSMD1	ENST00000520002.5	TSL:5	c.1010-9092A>G		intron	N/A	ENSP00000430733.1	E5RIG2
	CSMD1	ENST00000602557.5	TSL:5	c.1010-9092A>G		intron	N/A	ENSP00000473359.1	E5RIG2

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17259 AN: 152046 Hom.: 1273 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.0749

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0709

Gnomad FIN AF: 0.0651

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0913

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.114 AC: 17289 AN: 152164 Hom.: 1277 Cov.: 32 AF XY: 0.110 AC XY: 8169 AN XY: 74392

African (AFR) AF: 0.198 AC: 8215 AN: 41474

American (AMR) AF: 0.0747 AC: 1142 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 383 AN: 3470

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5180

South Asian (SAS) AF: 0.0709 AC: 342 AN: 4822

European-Finnish (FIN) AF: 0.0651 AC: 690 AN: 10602

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0913 AC: 6209 AN: 68004

Other (OTH) AF: 0.105 AC: 221 AN: 2112

Alfa AF: 0.0971 Hom.: 430

Bravo AF: 0.118

Asia WGS AF: 0.0460 AC: 161 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.68
DANN	Benign	0.41
PhyloP100		-0.48
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: rs2449222; hg19: chr8-3483411;