8-4442361-G-A

Variant names:

• chr8-4442361-G-A
• rs17070309
• NM_033225.6:c.303-22296C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033225.6(CSMD1):​c.303-22296C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,002 control chromosomes in the GnomAD database, including 2,495 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 0.17 (2495 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 7 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 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.303-22296C>T		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.303-22296C>T		intron	N/A	ENSP00000489225.1
	CSMD1	ENST00000520002.5	TSL:5	c.303-22296C>T		intron	N/A	ENSP00000430733.1
	CSMD1	ENST00000602557.5	TSL:5	c.303-22296C>T		intron	N/A	ENSP00000473359.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26035 AN: 151886 Hom.: 2494 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.171 AC: 26043 AN: 152002 Hom.: 2495 Cov.: 32 AF XY: 0.181 AC XY: 13409 AN XY: 74278

African (AFR) AF: 0.124 AC: 5159 AN: 41474

American (AMR) AF: 0.190 AC: 2898 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 682 AN: 3468

East Asian (EAS) AF: 0.378 AC: 1953 AN: 5160

South Asian (SAS) AF: 0.265 AC: 1275 AN: 4812

European-Finnish (FIN) AF: 0.271 AC: 2852 AN: 10528

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10677 AN: 67980

Other (OTH) AF: 0.156 AC: 329 AN: 2104

Alfa AF: 0.162 Hom.: 9577

Bravo AF: 0.165

Asia WGS AF: 0.280 AC: 972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.057
DANN	Benign	0.69
PhyloP100		-2.0
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: rs17070309; hg19: chr8-4299883;