rs9657371

Variant names:

• chr8-4925136-C-A
• rs9657371
• NM_033225.6:c.85+69196G>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.85+69196G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 151,132 control chromosomes in the GnomAD database, including 7,483 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 0.30 (7483 hom., cov: 30)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.85+69196G>T		intron_variant	Intron 1 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.85+69196G>T		intron_variant	Intron 1 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.85+69196G>T		intron_variant	Intron 1 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.85+69196G>T		intron_variant	Intron 1 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44776 AN: 151028 Hom.: 7487 Cov.: 30

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.0421

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.296 AC: 44804 AN: 151132 Hom.: 7483 Cov.: 30 AF XY: 0.293 AC XY: 21602 AN XY: 73680

African (AFR) AF: 0.171 AC: 7035 AN: 41168

American (AMR) AF: 0.271 AC: 4109 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1224 AN: 3464

East Asian (EAS) AF: 0.0422 AC: 217 AN: 5140

South Asian (SAS) AF: 0.274 AC: 1310 AN: 4784

European-Finnish (FIN) AF: 0.329 AC: 3365 AN: 10240

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26329 AN: 67854

Other (OTH) AF: 0.317 AC: 662 AN: 2088

Alfa AF: 0.358 Hom.: 45907

Bravo AF: 0.285

Asia WGS AF: 0.167 AC: 581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.38
PhyloP100		-0.22
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: rs9657371; hg19: chr8-4782658;