chr8-3584928-T-C

Variant names:

• chr8-3584928-T-C
• rs7013570
• NM_033225.6:c.1222+1208A>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.1222+1208A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0557 in 152,190 control chromosomes in the GnomAD database, including 279 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 0.056 (279 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.098 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.1222+1208A>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.1222+1208A>G		intron	N/A	ENSP00000489225.1	Q96PZ7-1
	CSMD1	ENST00000520002.5	TSL:5	c.1225+1208A>G		intron	N/A	ENSP00000430733.1	E5RIG2
	CSMD1	ENST00000602557.5	TSL:5	c.1225+1208A>G		intron	N/A	ENSP00000473359.1	E5RIG2

Frequencies

GnomAD3 genomes AF: 0.0557 AC: 8477 AN: 152072 Hom.: 281 Cov.: 32

Gnomad AFR AF: 0.0453

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.0616

Gnomad ASJ AF: 0.0456

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0905

Gnomad FIN AF: 0.0380

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.0571

Gnomad OTH AF: 0.0541

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

GnomAD4 genome AF: 0.0557 AC: 8479 AN: 152190 Hom.: 279 Cov.: 32 AF XY: 0.0564 AC XY: 4197 AN XY: 74414

African (AFR) AF: 0.0452 AC: 1879 AN: 41532

American (AMR) AF: 0.0618 AC: 944 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0456 AC: 158 AN: 3468

East Asian (EAS) AF: 0.105 AC: 544 AN: 5166

South Asian (SAS) AF: 0.0902 AC: 434 AN: 4814

European-Finnish (FIN) AF: 0.0380 AC: 403 AN: 10602

Middle Eastern (MID) AF: 0.0342 AC: 10 AN: 292

European-Non Finnish (NFE) AF: 0.0571 AC: 3883 AN: 68016

Other (OTH) AF: 0.0550 AC: 116 AN: 2110

Alfa AF: 0.0557 Hom.: 532

Bravo AF: 0.0565

Asia WGS AF: 0.119 AC: 414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.096
DANN	Benign	0.55
PhyloP100		-0.25
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: rs7013570; hg19: chr8-3442450;