chr8-3570011-A-G

Variant names:

• chr8-3570011-A-G
• rs995322
• NM_033225.6:c.1344+4934T>C

Variant summary

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

The NM_033225.6(CSMD1):​c.1344+4934T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,232 control chromosomes in the GnomAD database, including 57,135 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 0.86 (57135 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355
• Publications: 10 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 = 0.881 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	NM_033225.6	MANE Select	c.1344+4934T>C		intron	N/A	NP_150094.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	ENST00000635120.2	TSL:5 MANE Select	c.1344+4934T>C		intron	N/A	ENSP00000489225.1
	CSMD1	ENST00000520002.5	TSL:5	c.1347+4934T>C		intron	N/A	ENSP00000430733.1
	CSMD1	ENST00000602557.5	TSL:5	c.1347+4934T>C		intron	N/A	ENSP00000473359.1

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131446 AN: 152112 Hom.: 57109 Cov.: 33

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.831

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.903

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.851

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

GnomAD4 genome AF: 0.864 AC: 131528 AN: 152232 Hom.: 57135 Cov.: 33 AF XY: 0.862 AC XY: 64139 AN XY: 74422

African (AFR) AF: 0.867 AC: 36010 AN: 41542

American (AMR) AF: 0.859 AC: 13136 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 3045 AN: 3466

East Asian (EAS) AF: 0.590 AC: 3048 AN: 5162

South Asian (SAS) AF: 0.742 AC: 3579 AN: 4822

European-Finnish (FIN) AF: 0.903 AC: 9571 AN: 10602

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.887 AC: 60342 AN: 68022

Other (OTH) AF: 0.843 AC: 1784 AN: 2116

Alfa AF: 0.876 Hom.: 18637

Bravo AF: 0.860

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.58
DANN	Benign	0.46
PhyloP100		-0.35
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: rs995322; hg19: chr8-3427533;