rs718121

Variant names:

• chr8-3302039-T-C
• rs718121
• NM_033225.6:c.3950+5656A>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.3950+5656A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 151,900 control chromosomes in the GnomAD database, including 20,811 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 0.49 (20811 hom., cov: 30)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.00
• 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 (NFE) allele frequency at 95% confidence interval = 0.624 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.3950+5656A>G		intron	N/A	NP_150094.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	ENST00000635120.2	TSL:5 MANE Select	c.3950+5656A>G		intron	N/A	ENSP00000489225.1	Q96PZ7-1
	CSMD1	ENST00000335551.11	TSL:1	c.2390+5656A>G		intron	N/A	ENSP00000334828.6	H7BXU2
	CSMD1	ENST00000523488.5	TSL:1	n.1483+5656A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74508 AN: 151782 Hom.: 20822 Cov.: 30

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.490 AC: 74490 AN: 151900 Hom.: 20811 Cov.: 30 AF XY: 0.493 AC XY: 36564 AN XY: 74218

African (AFR) AF: 0.208 AC: 8632 AN: 41466

American (AMR) AF: 0.505 AC: 7712 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2157 AN: 3468

East Asian (EAS) AF: 0.378 AC: 1938 AN: 5126

South Asian (SAS) AF: 0.619 AC: 2973 AN: 4804

European-Finnish (FIN) AF: 0.612 AC: 6446 AN: 10534

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42758 AN: 67926

Other (OTH) AF: 0.509 AC: 1075 AN: 2114

Alfa AF: 0.592 Hom.: 14903

Bravo AF: 0.466

Asia WGS AF: 0.472 AC: 1645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0040
DANN	Benign	0.62
PhyloP100		-4.0
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: rs718121; hg19: chr8-3159561;