8-3332374-A-G

Variant names:

• chr8-3332374-A-G
• rs2551043
• NM_033225.6:c.3631+10920T>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.3631+10920T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,096 control chromosomes in the GnomAD database, including 15,101 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 0.42 (15101 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 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.3631+10920T>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.3631+10920T>C		intron	N/A	ENSP00000489225.1
	CSMD1	ENST00000335551.11	TSL:1	c.2071+10920T>C		intron	N/A	ENSP00000334828.6
	CSMD1	ENST00000523488.5	TSL:1	n.1164+10920T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64618 AN: 151978 Hom.: 15101 Cov.: 33

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.425 AC: 64626 AN: 152096 Hom.: 15101 Cov.: 33 AF XY: 0.427 AC XY: 31712 AN XY: 74352

African (AFR) AF: 0.244 AC: 10145 AN: 41514

American (AMR) AF: 0.343 AC: 5243 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1683 AN: 3470

East Asian (EAS) AF: 0.351 AC: 1806 AN: 5138

South Asian (SAS) AF: 0.492 AC: 2372 AN: 4826

European-Finnish (FIN) AF: 0.569 AC: 6019 AN: 10582

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.527 AC: 35810 AN: 67964

Other (OTH) AF: 0.416 AC: 879 AN: 2114

Alfa AF: 0.491 Hom.: 80451

Bravo AF: 0.397

Asia WGS AF: 0.376 AC: 1307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.71
PhyloP100		1.4
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: rs2551043; hg19: chr8-3189896;