8-3663349-T-C

Variant names:

• chr8-3663349-T-C
• rs2624087
• NM_033225.6:c.1009+45065A>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.1009+45065A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,042 control chromosomes in the GnomAD database, including 7,519 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 0.31 (7519 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48
• 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.1009+45065A>G		intron_variant	Intron 7 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.1009+45065A>G		intron_variant	Intron 7 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.1009+45065A>G		intron_variant	Intron 7 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.1009+45065A>G		intron_variant	Intron 7 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47037 AN: 151924 Hom.: 7509 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.310 AC: 47083 AN: 152042 Hom.: 7519 Cov.: 32 AF XY: 0.304 AC XY: 22600 AN XY: 74326

African (AFR) AF: 0.354 AC: 14680 AN: 41454

American (AMR) AF: 0.255 AC: 3891 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1171 AN: 3468

East Asian (EAS) AF: 0.112 AC: 581 AN: 5170

South Asian (SAS) AF: 0.312 AC: 1502 AN: 4812

European-Finnish (FIN) AF: 0.264 AC: 2796 AN: 10578

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21594 AN: 67970

Other (OTH) AF: 0.315 AC: 663 AN: 2106

Alfa AF: 0.314 Hom.: 32694

Bravo AF: 0.310

Asia WGS AF: 0.213 AC: 742 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	0.11
DANN	Benign	0.35
PhyloP100		-2.5
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: rs2624087; hg19: chr8-3520871;