8-3853512-A-C

Variant names:

• chr8-3853512-A-C
• rs2930355
• NM_033225.6:c.819-99470T>G

Variant summary

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

The NM_033225.6(CSMD1):​c.819-99470T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,182 control chromosomes in the GnomAD database, including 3,149 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 0.19 (3149 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308
• Publications: 1 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.819-99470T>G		intron_variant	Intron 5 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.819-99470T>G		intron_variant	Intron 5 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.819-99470T>G		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.819-99470T>G		intron_variant	Intron 5 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29556 AN: 152064 Hom.: 3146 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.194 AC: 29585 AN: 152182 Hom.: 3149 Cov.: 32 AF XY: 0.193 AC XY: 14338 AN XY: 74402

African (AFR) AF: 0.235 AC: 9771 AN: 41502

American (AMR) AF: 0.203 AC: 3104 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 552 AN: 3470

East Asian (EAS) AF: 0.420 AC: 2174 AN: 5180

South Asian (SAS) AF: 0.206 AC: 990 AN: 4816

European-Finnish (FIN) AF: 0.102 AC: 1084 AN: 10602

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11273 AN: 68004

Other (OTH) AF: 0.210 AC: 445 AN: 2116

Alfa AF: 0.182 Hom.: 8363

Bravo AF: 0.205

Asia WGS AF: 0.323 AC: 1122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.45
PhyloP100		-0.31
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: rs2930355; hg19: chr8-3711034;