8-3358503-T-G

Variant names:

• chr8-3358503-T-G
• rs9773092
• NM_033225.6:c.3304+649A>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.3304+649A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,084 control chromosomes in the GnomAD database, including 6,395 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 0.28 (6395 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 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.3304+649A>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.3304+649A>C		intron	N/A	ENSP00000489225.1
	CSMD1	ENST00000335551.11	TSL:1	c.1744+649A>C		intron	N/A	ENSP00000334828.6
	CSMD1	ENST00000523488.5	TSL:1	n.837+649A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42834 AN: 151968 Hom.: 6383 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.282 AC: 42884 AN: 152084 Hom.: 6395 Cov.: 32 AF XY: 0.276 AC XY: 20491 AN XY: 74340

African (AFR) AF: 0.385 AC: 15972 AN: 41462

American (AMR) AF: 0.316 AC: 4831 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 823 AN: 3468

East Asian (EAS) AF: 0.327 AC: 1690 AN: 5166

South Asian (SAS) AF: 0.194 AC: 938 AN: 4830

European-Finnish (FIN) AF: 0.161 AC: 1709 AN: 10590

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16070 AN: 67978

Other (OTH) AF: 0.282 AC: 596 AN: 2114

Alfa AF: 0.226 Hom.: 2310

Bravo AF: 0.305

Asia WGS AF: 0.263 AC: 914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.048
DANN	Benign	0.42
PhyloP100		-1.1
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: rs9773092; hg19: chr8-3216025; COSMIC: COSV59338107;