chr8-4085605-G-C

Variant names:

• chr8-4085605-G-C
• rs9644362
• NM_033225.6:c.416-53506C>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.416-53506C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,124 control chromosomes in the GnomAD database, including 2,255 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 0.16 (2255 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.324 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.416-53506C>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.416-53506C>G		intron	N/A	ENSP00000489225.1
	CSMD1	ENST00000520002.5	TSL:5	c.416-53506C>G		intron	N/A	ENSP00000430733.1
	CSMD1	ENST00000602557.5	TSL:5	c.416-53506C>G		intron	N/A	ENSP00000473359.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24512 AN: 152006 Hom.: 2256 Cov.: 32

Gnomad AFR AF: 0.0798

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.161 AC: 24512 AN: 152124 Hom.: 2255 Cov.: 32 AF XY: 0.165 AC XY: 12244 AN XY: 74366

African (AFR) AF: 0.0797 AC: 3311 AN: 41520

American (AMR) AF: 0.151 AC: 2308 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 633 AN: 3470

East Asian (EAS) AF: 0.237 AC: 1220 AN: 5158

South Asian (SAS) AF: 0.338 AC: 1630 AN: 4824

European-Finnish (FIN) AF: 0.218 AC: 2304 AN: 10562

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.186 AC: 12650 AN: 67988

Other (OTH) AF: 0.150 AC: 315 AN: 2104

Alfa AF: 0.168 Hom.: 297

Bravo AF: 0.147

Asia WGS AF: 0.239 AC: 829 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	1.8
DANN	Benign	0.44
PhyloP100		0.43
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: rs9644362; hg19: chr8-3943127;