NM_033225.6:c.302+11723T>C

Variant names:

• chr8-4625619-A-G
• rs2616984
• NM_033225.6:c.302+11723T>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.302+11723T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,888 control chromosomes in the GnomAD database, including 6,853 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 0.29 (6853 hom., cov: 31)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.317 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.302+11723T>C		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.302+11723T>C		intron	N/A	ENSP00000489225.1
	CSMD1	ENST00000520002.5	TSL:5	c.302+11723T>C		intron	N/A	ENSP00000430733.1
	CSMD1	ENST00000602557.5	TSL:5	c.302+11723T>C		intron	N/A	ENSP00000473359.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44182 AN: 151770 Hom.: 6846 Cov.: 31

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.00387

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.291 AC: 44217 AN: 151888 Hom.: 6853 Cov.: 31 AF XY: 0.287 AC XY: 21264 AN XY: 74194

African (AFR) AF: 0.303 AC: 12566 AN: 41426

American (AMR) AF: 0.240 AC: 3659 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1002 AN: 3468

East Asian (EAS) AF: 0.00349 AC: 18 AN: 5156

South Asian (SAS) AF: 0.222 AC: 1068 AN: 4804

European-Finnish (FIN) AF: 0.286 AC: 3012 AN: 10536

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.321 AC: 21800 AN: 67932

Other (OTH) AF: 0.332 AC: 699 AN: 2106

Alfa AF: 0.309 Hom.: 7278

Bravo AF: 0.286

Asia WGS AF: 0.114 AC: 400 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	0.32
DANN	Benign	0.37
PhyloP100		-0.085
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: rs2616984; hg19: chr8-4483141;