rs2449213

Variant names:

• chr8-3659787-G-A
• rs2449213
• NM_033225.6:c.1010-42990C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-3659787-G-A
• chr8-3659787-G-T

Variant summary

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

The NM_033225.6(CSMD1):​c.1010-42990C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0784 in 151,990 control chromosomes in the GnomAD database, including 1,307 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 0.078 (1307 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.550
• Publications: 0 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.1010-42990C>T		intron_variant	Intron 7 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.1010-42990C>T		intron_variant	Intron 7 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.1010-42990C>T		intron_variant	Intron 7 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.1010-42990C>T		intron_variant	Intron 7 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.0783 AC: 11894 AN: 151872 Hom.: 1303 Cov.: 33

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0303

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0589

Gnomad SAS AF: 0.0502

Gnomad FIN AF: 0.0204

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00488

Gnomad OTH AF: 0.0545

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

GnomAD4 genome AF: 0.0784 AC: 11923 AN: 151990 Hom.: 1307 Cov.: 33 AF XY: 0.0776 AC XY: 5763 AN XY: 74278

African (AFR) AF: 0.247 AC: 10234 AN: 41436

American (AMR) AF: 0.0303 AC: 462 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.0593 AC: 306 AN: 5162

South Asian (SAS) AF: 0.0490 AC: 236 AN: 4816

European-Finnish (FIN) AF: 0.0204 AC: 215 AN: 10546

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00488 AC: 332 AN: 67970

Other (OTH) AF: 0.0558 AC: 118 AN: 2114

Alfa AF: 0.0206 Hom.: 90

Bravo AF: 0.0865

Asia WGS AF: 0.0700 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.7
DANN	Benign	0.55
PhyloP100		0.55
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: rs2449213; hg19: chr8-3517309;