rs17390295

Variant names:

• chr8-3101140-G-A
• rs17390295
• NM_033225.6:c.6950-4103C>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.6950-4103C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0409 in 150,612 control chromosomes in the GnomAD database, including 153 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 0.041 (153 hom., cov: 30)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400
• Publications: 6 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.6950-4103C>T		intron_variant	Intron 46 of 69	ENST00000635120.2	NP_150094.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.6950-4103C>T		intron_variant	Intron 46 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 6150 AN: 150502 Hom.: 152 Cov.: 30

Gnomad AFR AF: 0.00919

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.0685

Gnomad ASJ AF: 0.0447

Gnomad EAS AF: 0.0527

Gnomad SAS AF: 0.0408

Gnomad FIN AF: 0.0363

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.0533

Gnomad OTH AF: 0.0480

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

GnomAD4 genome AF: 0.0409 AC: 6154 AN: 150612 Hom.: 153 Cov.: 30 AF XY: 0.0408 AC XY: 2992 AN XY: 73406

African (AFR) AF: 0.00916 AC: 375 AN: 40934

American (AMR) AF: 0.0687 AC: 1037 AN: 15100

Ashkenazi Jewish (ASJ) AF: 0.0447 AC: 155 AN: 3470

East Asian (EAS) AF: 0.0528 AC: 268 AN: 5072

South Asian (SAS) AF: 0.0406 AC: 193 AN: 4748

European-Finnish (FIN) AF: 0.0363 AC: 368 AN: 10150

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.0533 AC: 3617 AN: 67854

Other (OTH) AF: 0.0476 AC: 99 AN: 2082

Alfa AF: 0.0468 Hom.: 189

Bravo AF: 0.0424

Asia WGS AF: 0.0590 AC: 206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.89
DANN	Benign	0.43
PhyloP100		-0.40
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: rs17390295; hg19: chr8-2958662;