NM_033225.6:c.416-188732C>G

Variant names:

• chr8-4220831-G-C
• rs2407314
• NM_033225.6:c.416-188732C>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.416-188732C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,072 control chromosomes in the GnomAD database, including 15,937 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 0.45 (15937 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.631 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	NM_033225.6	MANE Select	c.416-188732C>G		intron	N/A	NP_150094.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	ENST00000635120.2	TSL:5 MANE Select	c.416-188732C>G		intron	N/A	ENSP00000489225.1
	CSMD1	ENST00000520002.5	TSL:5	c.416-188732C>G		intron	N/A	ENSP00000430733.1
	CSMD1	ENST00000602557.5	TSL:5	c.416-188732C>G		intron	N/A	ENSP00000473359.1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67660 AN: 151952 Hom.: 15911 Cov.: 32

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.445 AC: 67738 AN: 152072 Hom.: 15937 Cov.: 32 AF XY: 0.449 AC XY: 33405 AN XY: 74350

African (AFR) AF: 0.557 AC: 23128 AN: 41486

American (AMR) AF: 0.527 AC: 8043 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1517 AN: 3472

East Asian (EAS) AF: 0.410 AC: 2112 AN: 5146

South Asian (SAS) AF: 0.650 AC: 3130 AN: 4814

European-Finnish (FIN) AF: 0.297 AC: 3139 AN: 10586

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25144 AN: 67972

Other (OTH) AF: 0.458 AC: 968 AN: 2114

Alfa AF: 0.359 Hom.: 5283

Bravo AF: 0.461

Asia WGS AF: 0.514 AC: 1790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.027
DANN	Benign	0.65
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: rs2407314; hg19: chr8-4078353;