chr8-4459824-G-T

Variant names:

• chr8-4459824-G-T
• rs1217675
• NM_033225.6:c.303-39759C>A

Variant summary

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

The NM_033225.6(CSMD1):​c.303-39759C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,040 control chromosomes in the GnomAD database, including 6,432 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 0.27 (6432 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.926
• Publications: 2 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.303-39759C>A		intron_variant	Intron 2 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.303-39759C>A		intron_variant	Intron 2 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.303-39759C>A		intron_variant	Intron 2 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.303-39759C>A		intron_variant	Intron 2 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41383 AN: 151922 Hom.: 6422 Cov.: 33

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.0657

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.273 AC: 41431 AN: 152040 Hom.: 6432 Cov.: 33 AF XY: 0.271 AC XY: 20144 AN XY: 74312

African (AFR) AF: 0.416 AC: 17265 AN: 41456

American (AMR) AF: 0.194 AC: 2969 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 624 AN: 3472

East Asian (EAS) AF: 0.0660 AC: 341 AN: 5166

South Asian (SAS) AF: 0.120 AC: 576 AN: 4816

European-Finnish (FIN) AF: 0.330 AC: 3485 AN: 10570

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15412 AN: 67962

Other (OTH) AF: 0.248 AC: 524 AN: 2112

Alfa AF: 0.229 Hom.: 8530

Bravo AF: 0.269

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.59
DANN	Benign	0.32
PhyloP100		-0.93
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: rs1217675; hg19: chr8-4317346;