8-4252510-T-C

Variant names:

• chr8-4252510-T-C
• rs13259289
• NM_033225.6:c.415+167443A>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.415+167443A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,132 control chromosomes in the GnomAD database, including 7,862 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 0.29 (7862 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.396 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.415+167443A>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.415+167443A>G		intron	N/A	ENSP00000489225.1
	CSMD1	ENST00000520002.5	TSL:5	c.415+167443A>G		intron	N/A	ENSP00000430733.1
	CSMD1	ENST00000602557.5	TSL:5	c.415+167443A>G		intron	N/A	ENSP00000473359.1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44137 AN: 152014 Hom.: 7865 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.00482

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.290 AC: 44140 AN: 152132 Hom.: 7862 Cov.: 33 AF XY: 0.287 AC XY: 21315 AN XY: 74378

African (AFR) AF: 0.115 AC: 4767 AN: 41548

American (AMR) AF: 0.314 AC: 4803 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1259 AN: 3466

East Asian (EAS) AF: 0.00502 AC: 26 AN: 5180

South Asian (SAS) AF: 0.134 AC: 646 AN: 4828

European-Finnish (FIN) AF: 0.409 AC: 4323 AN: 10562

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27188 AN: 67942

Other (OTH) AF: 0.294 AC: 622 AN: 2116

Alfa AF: 0.360 Hom.: 19269

Bravo AF: 0.279

Asia WGS AF: 0.0830 AC: 287 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	0.80
DANN	Benign	0.77
PhyloP100		-0.24
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: rs13259289; hg19: chr8-4110032;