rs7827348

Variant names:

• chr8-3175293-T-C
• rs7827348
• NM_033225.6:c.5725+5817A>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.5725+5817A>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 152,070 control chromosomes in the GnomAD database, including 9,001 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 (9001 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.5725+5817A>G		intron_variant	Intron 37 of 69	ENST00000635120.2	NP_150094.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.5725+5817A>G		intron_variant	Intron 37 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46989 AN: 151950 Hom.: 8972 Cov.: 32

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.310 AC: 47071 AN: 152070 Hom.: 9001 Cov.: 32 AF XY: 0.311 AC XY: 23132 AN XY: 74338

African (AFR) AF: 0.516 AC: 21386 AN: 41452

American (AMR) AF: 0.269 AC: 4113 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 883 AN: 3472

East Asian (EAS) AF: 0.564 AC: 2920 AN: 5174

South Asian (SAS) AF: 0.440 AC: 2123 AN: 4824

European-Finnish (FIN) AF: 0.165 AC: 1744 AN: 10576

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13057 AN: 67980

Other (OTH) AF: 0.289 AC: 609 AN: 2110

Alfa AF: 0.225 Hom.: 7783

Bravo AF: 0.323

Asia WGS AF: 0.530 AC: 1842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.6
DANN	Benign	0.46
PhyloP100		-0.12
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: rs7827348; hg19: chr8-3032815;