8-3859946-A-G

Variant names:

• chr8-3859946-A-G
• rs2930353
• NM_033225.6:c.819-105904T>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.819-105904T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 151,958 control chromosomes in the GnomAD database, including 12,128 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 0.39 (12128 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.432
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.819-105904T>C		intron_variant	Intron 5 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.819-105904T>C		intron_variant	Intron 5 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.819-105904T>C		intron_variant	Intron 5 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.819-105904T>C		intron_variant	Intron 5 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59386 AN: 151838 Hom.: 12103 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.391 AC: 59453 AN: 151958 Hom.: 12128 Cov.: 32 AF XY: 0.387 AC XY: 28714 AN XY: 74260

African (AFR) AF: 0.486 AC: 20129 AN: 41420

American (AMR) AF: 0.374 AC: 5702 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1586 AN: 3468

East Asian (EAS) AF: 0.477 AC: 2455 AN: 5144

South Asian (SAS) AF: 0.456 AC: 2198 AN: 4822

European-Finnish (FIN) AF: 0.259 AC: 2737 AN: 10566

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23444 AN: 67966

Other (OTH) AF: 0.416 AC: 877 AN: 2106

Alfa AF: 0.365 Hom.: 39571

Bravo AF: 0.402

Asia WGS AF: 0.500 AC: 1739 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	0.74
DANN	Benign	0.51
PhyloP100		-0.43
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: rs2930353; hg19: chr8-3717468;