8-4609812-G-T

Variant names:

• chr8-4609812-G-T
• rs2725045
• NM_033225.6:c.302+27530C>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.302+27530C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 151,958 control chromosomes in the GnomAD database, including 10,737 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 0.36 (10737 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• 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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.53 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.302+27530C>A		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.302+27530C>A		intron	N/A	ENSP00000489225.1
	CSMD1	ENST00000520002.5	TSL:5	c.302+27530C>A		intron	N/A	ENSP00000430733.1
	CSMD1	ENST00000602557.5	TSL:5	c.302+27530C>A		intron	N/A	ENSP00000473359.1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54422 AN: 151840 Hom.: 10712 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.359 AC: 54500 AN: 151958 Hom.: 10737 Cov.: 32 AF XY: 0.355 AC XY: 26377 AN XY: 74264

African (AFR) AF: 0.535 AC: 22198 AN: 41458

American (AMR) AF: 0.256 AC: 3914 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1297 AN: 3470

East Asian (EAS) AF: 0.290 AC: 1491 AN: 5146

South Asian (SAS) AF: 0.297 AC: 1428 AN: 4812

European-Finnish (FIN) AF: 0.287 AC: 3025 AN: 10552

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20072 AN: 67926

Other (OTH) AF: 0.361 AC: 763 AN: 2112

Alfa AF: 0.292 Hom.: 4349

Bravo AF: 0.365

Asia WGS AF: 0.290 AC: 1010 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.16
DANN	Benign	0.29
PhyloP100		-2.3
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: rs2725045; hg19: chr8-4467334;