8-4044980-A-T

Variant names:

• chr8-4044980-A-T
• rs9772485
• NM_033225.6:c.416-12881T>A

Variant summary

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

The NM_033225.6(CSMD1):​c.416-12881T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,106 control chromosomes in the GnomAD database, including 5,447 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 0.27 (5447 hom., cov: 34)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.14
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.286 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.416-12881T>A		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.416-12881T>A		intron	N/A	ENSP00000489225.1	Q96PZ7-1
	CSMD1	ENST00000520002.5	TSL:5	c.416-12881T>A		intron	N/A	ENSP00000430733.1	E5RIG2
	CSMD1	ENST00000602557.5	TSL:5	c.416-12881T>A		intron	N/A	ENSP00000473359.1	E5RIG2

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40450 AN: 151988 Hom.: 5442 Cov.: 34

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.266 AC: 40490 AN: 152106 Hom.: 5447 Cov.: 34 AF XY: 0.263 AC XY: 19559 AN XY: 74356

African (AFR) AF: 0.282 AC: 11701 AN: 41476

American (AMR) AF: 0.294 AC: 4487 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 802 AN: 3468

East Asian (EAS) AF: 0.213 AC: 1099 AN: 5170

South Asian (SAS) AF: 0.200 AC: 966 AN: 4818

European-Finnish (FIN) AF: 0.220 AC: 2329 AN: 10592

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18200 AN: 67978

Other (OTH) AF: 0.275 AC: 581 AN: 2112

Alfa AF: 0.156 Hom.: 281

Bravo AF: 0.271

Asia WGS AF: 0.230 AC: 795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.72
DANN	Benign	0.69
PhyloP100		-3.1
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: rs9772485; hg19: chr8-3902502;