8-2962287-T-C

Variant names:

• chr8-2962287-T-C
• rs4875857
• NM_033225.6:c.9628+179A>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.9628+179A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,152 control chromosomes in the GnomAD database, including 8,627 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 0.29 (8627 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.16
• Publications: 9 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

LOC105377785 (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 = 0.547 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.9628+179A>G		intron	N/A	NP_150094.5
	LOC105377785	NR_168441.1		n.1167-38718T>C		intron	N/A
	LOC105377785	NR_168442.1		n.2191+35657T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	ENST00000635120.2	TSL:5 MANE Select	c.9628+179A>G		intron	N/A	ENSP00000489225.1
	CSMD1	ENST00000335551.11	TSL:1	c.7879+179A>G		intron	N/A	ENSP00000334828.6
	CSMD1	ENST00000520002.5	TSL:5	c.9631+179A>G		intron	N/A	ENSP00000430733.1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44667 AN: 152034 Hom.: 8603 Cov.: 33

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.294 AC: 44746 AN: 152152 Hom.: 8627 Cov.: 33 AF XY: 0.294 AC XY: 21854 AN XY: 74398

African (AFR) AF: 0.553 AC: 22925 AN: 41486

American (AMR) AF: 0.269 AC: 4112 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 604 AN: 3472

East Asian (EAS) AF: 0.256 AC: 1325 AN: 5174

South Asian (SAS) AF: 0.158 AC: 763 AN: 4828

European-Finnish (FIN) AF: 0.212 AC: 2248 AN: 10596

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.175 AC: 11870 AN: 67994

Other (OTH) AF: 0.256 AC: 541 AN: 2110

Alfa AF: 0.207 Hom.: 17411

Bravo AF: 0.309

Asia WGS AF: 0.222 AC: 770 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	0.073
DANN	Benign	0.43
PhyloP100		-4.2
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: rs4875857; hg19: chr8-2819809;