8-4326438-A-T

Variant names:

• chr8-4326438-A-T
• rs9314525
• NM_033225.6:c.415+93515T>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.415+93515T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,062 control chromosomes in the GnomAD database, including 4,563 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 0.24 (4563 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537
• 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

ENSG00000286934 (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.415+93515T>A		intron_variant	Intron 3 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.415+93515T>A		intron_variant	Intron 3 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.415+93515T>A		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.415+93515T>A		intron_variant	Intron 3 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35844 AN: 151944 Hom.: 4561 Cov.: 33

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.236 AC: 35868 AN: 152062 Hom.: 4563 Cov.: 33 AF XY: 0.242 AC XY: 17991 AN XY: 74316

African (AFR) AF: 0.279 AC: 11581 AN: 41462

American (AMR) AF: 0.149 AC: 2282 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 675 AN: 3466

East Asian (EAS) AF: 0.330 AC: 1702 AN: 5152

South Asian (SAS) AF: 0.379 AC: 1826 AN: 4818

European-Finnish (FIN) AF: 0.318 AC: 3359 AN: 10570

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13736 AN: 67982

Other (OTH) AF: 0.230 AC: 486 AN: 2114

Alfa AF: 0.112 Hom.: 200

Bravo AF: 0.219

Asia WGS AF: 0.370 AC: 1288 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.55
DANN	Benign	0.55
PhyloP100		-0.54
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: rs9314525; hg19: chr8-4183960;