chr8-4184298-A-G

Variant names:

• chr8-4184298-A-G
• rs17069238
• NM_033225.6:c.416-152199T>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.416-152199T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0547 in 152,254 control chromosomes in the GnomAD database, including 309 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 0.055 (309 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• Publications: 0 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.416-152199T>C		intron_variant	Intron 3 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.416-152199T>C		intron_variant	Intron 3 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.416-152199T>C		intron_variant	Intron 3 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.416-152199T>C		intron_variant	Intron 3 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.0547 AC: 8321 AN: 152136 Hom.: 309 Cov.: 33

Gnomad AFR AF: 0.0955

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0329

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0386

Gnomad FIN AF: 0.0427

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0442

Gnomad OTH AF: 0.0492

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

GnomAD4 genome AF: 0.0547 AC: 8327 AN: 152254 Hom.: 309 Cov.: 33 AF XY: 0.0536 AC XY: 3993 AN XY: 74438

African (AFR) AF: 0.0954 AC: 3962 AN: 41542

American (AMR) AF: 0.0328 AC: 502 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0297 AC: 103 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.0382 AC: 184 AN: 4820

European-Finnish (FIN) AF: 0.0427 AC: 453 AN: 10604

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0442 AC: 3008 AN: 68026

Other (OTH) AF: 0.0487 AC: 103 AN: 2114

Alfa AF: 0.0492 Hom.: 40

Bravo AF: 0.0544

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.47
DANN	Benign	0.53
PhyloP100		-0.055
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: rs17069238; hg19: chr8-4041820;