8-4310086-T-G

Variant names:

• chr8-4310086-T-G
• rs4875322
• NM_033225.6:c.415+109867A>C

Variant summary

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

The NM_033225.6(CSMD1):​c.415+109867A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 152,148 control chromosomes in the GnomAD database, including 49,626 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 0.80 (49626 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.892 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.415+109867A>C		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.415+109867A>C		intron	N/A	ENSP00000489225.1
	CSMD1	ENST00000520002.5	TSL:5	c.415+109867A>C		intron	N/A	ENSP00000430733.1
	CSMD1	ENST00000602557.5	TSL:5	c.415+109867A>C		intron	N/A	ENSP00000473359.1

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122304 AN: 152028 Hom.: 49567 Cov.: 32

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.796

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

GnomAD4 genome AF: 0.805 AC: 122419 AN: 152148 Hom.: 49626 Cov.: 32 AF XY: 0.805 AC XY: 59857 AN XY: 74364

African (AFR) AF: 0.900 AC: 37359 AN: 41532

American (AMR) AF: 0.855 AC: 13062 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2542 AN: 3470

East Asian (EAS) AF: 0.866 AC: 4481 AN: 5174

South Asian (SAS) AF: 0.757 AC: 3649 AN: 4822

European-Finnish (FIN) AF: 0.743 AC: 7863 AN: 10578

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.748 AC: 50860 AN: 67980

Other (OTH) AF: 0.795 AC: 1678 AN: 2110

Alfa AF: 0.767 Hom.: 73130

Bravo AF: 0.821

Asia WGS AF: 0.805 AC: 2798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.38
PhyloP100		-0.81
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: rs4875322; hg19: chr8-4167608;