8-4086560-G-C

Variant names:

• chr8-4086560-G-C
• rs10503232
• NM_033225.6:c.416-54461C>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.416-54461C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,200 control chromosomes in the GnomAD database, including 970 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 0.11 (970 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.123 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.416-54461C>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.416-54461C>G		intron	N/A	ENSP00000489225.1
	CSMD1	ENST00000520002.5	TSL:5	c.416-54461C>G		intron	N/A	ENSP00000430733.1
	CSMD1	ENST00000602557.5	TSL:5	c.416-54461C>G		intron	N/A	ENSP00000473359.1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16328 AN: 152082 Hom.: 973 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.0905

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0237

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0943

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.107 AC: 16337 AN: 152200 Hom.: 970 Cov.: 33 AF XY: 0.106 AC XY: 7891 AN XY: 74396

African (AFR) AF: 0.107 AC: 4462 AN: 41522

American (AMR) AF: 0.0904 AC: 1382 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3468

East Asian (EAS) AF: 0.0238 AC: 123 AN: 5174

South Asian (SAS) AF: 0.131 AC: 632 AN: 4826

European-Finnish (FIN) AF: 0.0943 AC: 999 AN: 10596

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7806 AN: 68014

Other (OTH) AF: 0.123 AC: 259 AN: 2106

Alfa AF: 0.0437 Hom.: 40

Bravo AF: 0.107

Asia WGS AF: 0.0880 AC: 307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.7
DANN	Benign	0.60
PhyloP100		0.31
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: rs10503232; hg19: chr8-3944082;