8-3235672-G-T

Variant names:

• chr8-3235672-G-T
• rs7814326
• NM_033225.6:c.4154-5441C>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.4154-5441C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,054 control chromosomes in the GnomAD database, including 5,457 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 0.26 (5457 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• Publications: 5 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 (SAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.4154-5441C>A		intron_variant	Intron 26 of 69	ENST00000635120.2	NP_150094.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.4154-5441C>A		intron_variant	Intron 26 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39662 AN: 151936 Hom.: 5455 Cov.: 33

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.0914

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.261 AC: 39695 AN: 152054 Hom.: 5457 Cov.: 33 AF XY: 0.263 AC XY: 19523 AN XY: 74318

African (AFR) AF: 0.340 AC: 14088 AN: 41476

American (AMR) AF: 0.207 AC: 3157 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 886 AN: 3468

East Asian (EAS) AF: 0.112 AC: 580 AN: 5164

South Asian (SAS) AF: 0.405 AC: 1948 AN: 4810

European-Finnish (FIN) AF: 0.244 AC: 2578 AN: 10560

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15810 AN: 67984

Other (OTH) AF: 0.233 AC: 493 AN: 2112

Alfa AF: 0.229 Hom.: 7055

Bravo AF: 0.254

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.8
DANN	Benign	0.66
PhyloP100		0.30
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: rs7814326; hg19: chr8-3093194;