NM_033225.6:c.302+7972T>C

Variant names:

• chr8-4629370-A-G
• rs1382259
• NM_033225.6:c.302+7972T>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+7972T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,126 control chromosomes in the GnomAD database, including 2,370 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 0.18 (2370 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.466
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.217 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+7972T>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+7972T>C		intron	N/A	ENSP00000489225.1	Q96PZ7-1
	CSMD1	ENST00000520002.5	TSL:5	c.302+7972T>C		intron	N/A	ENSP00000430733.1	E5RIG2
	CSMD1	ENST00000602557.5	TSL:5	c.302+7972T>C		intron	N/A	ENSP00000473359.1	E5RIG2

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26624 AN: 152010 Hom.: 2366 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.175 AC: 26644 AN: 152126 Hom.: 2370 Cov.: 33 AF XY: 0.172 AC XY: 12782 AN XY: 74370

African (AFR) AF: 0.193 AC: 8015 AN: 41490

American (AMR) AF: 0.124 AC: 1892 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3472

East Asian (EAS) AF: 0.150 AC: 778 AN: 5176

South Asian (SAS) AF: 0.228 AC: 1100 AN: 4826

European-Finnish (FIN) AF: 0.154 AC: 1635 AN: 10584

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12101 AN: 67980

Other (OTH) AF: 0.184 AC: 389 AN: 2110

Alfa AF: 0.172 Hom.: 1711

Bravo AF: 0.172

Asia WGS AF: 0.203 AC: 704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.3
DANN	Benign	0.57
PhyloP100		0.47
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: rs1382259; hg19: chr8-4486892;