rs865303

Variant names:

• chr8-2954749-C-A
• rs865303
• NM_033225.6:c.9995-481G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-2954749-C-A
• chr8-2954749-C-G
• chr8-2954749-C-T

Variant summary

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

The NM_033225.6(CSMD1):​c.9995-481G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,196 control chromosomes in the GnomAD database, including 46,900 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 0.78 (46900 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206
• 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

LOC105377785 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033225.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	NM_033225.6	MANE Select	c.9995-481G>T		intron	N/A	NP_150094.5
	LOC105377785	NR_168441.1		n.1167-46256C>A		intron	N/A
	LOC105377785	NR_168442.1		n.2191+28119C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	ENST00000635120.2	TSL:5 MANE Select	c.9995-481G>T		intron	N/A	ENSP00000489225.1	Q96PZ7-1
	CSMD1	ENST00000335551.11	TSL:1	c.8245+840G>T		intron	N/A	ENSP00000334828.6	H7BXU2
	CSMD1	ENST00000520002.5	TSL:5	c.9998-481G>T		intron	N/A	ENSP00000430733.1	E5RIG2

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119129 AN: 152078 Hom.: 46864 Cov.: 33

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.783 AC: 119214 AN: 152196 Hom.: 46900 Cov.: 33 AF XY: 0.786 AC XY: 58470 AN XY: 74414

African (AFR) AF: 0.801 AC: 33264 AN: 41510

American (AMR) AF: 0.702 AC: 10736 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2555 AN: 3470

East Asian (EAS) AF: 0.791 AC: 4102 AN: 5186

South Asian (SAS) AF: 0.711 AC: 3430 AN: 4824

European-Finnish (FIN) AF: 0.853 AC: 9047 AN: 10600

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.788 AC: 53592 AN: 68006

Other (OTH) AF: 0.749 AC: 1581 AN: 2110

Alfa AF: 0.778 Hom.: 72739

Bravo AF: 0.773

Asia WGS AF: 0.696 AC: 2420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.25
DANN	Benign	0.39
PhyloP100		0.21
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: rs865303; hg19: chr8-2812271;