8-3341005-T-C

Variant names:

• chr8-3341005-T-C
• rs10503204
• NM_033225.6:c.3631+2289A>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.3631+2289A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0393 in 152,314 control chromosomes in the GnomAD database, including 169 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 0.039 (169 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0767 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+2289A>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.3631+2289A>G		intron	N/A	ENSP00000489225.1
	CSMD1	ENST00000335551.11	TSL:1	c.2071+2289A>G		intron	N/A	ENSP00000334828.6
	CSMD1	ENST00000523488.5	TSL:1	n.1164+2289A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0393 AC: 5982 AN: 152196 Hom.: 171 Cov.: 33

Gnomad AFR AF: 0.0587

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0708

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.0832

Gnomad SAS AF: 0.0132

Gnomad FIN AF: 0.0265

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0221

Gnomad OTH AF: 0.0396

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

GnomAD4 genome AF: 0.0393 AC: 5992 AN: 152314 Hom.: 169 Cov.: 33 AF XY: 0.0401 AC XY: 2984 AN XY: 74474

African (AFR) AF: 0.0586 AC: 2437 AN: 41570

American (AMR) AF: 0.0713 AC: 1090 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3470

East Asian (EAS) AF: 0.0832 AC: 431 AN: 5180

South Asian (SAS) AF: 0.0128 AC: 62 AN: 4830

European-Finnish (FIN) AF: 0.0265 AC: 281 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0221 AC: 1505 AN: 68026

Other (OTH) AF: 0.0397 AC: 84 AN: 2116

Alfa AF: 0.0324 Hom.: 34

Bravo AF: 0.0432

Asia WGS AF: 0.0410 AC: 142 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	0.67
DANN	Benign	0.49
PhyloP100		-1.6
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: rs10503204; hg19: chr8-3198527;