8-4634987-T-C

Variant names:

• chr8-4634987-T-C
• rs4875371
• NM_033225.6:c.302+2355A>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.302+2355A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,204 control chromosomes in the GnomAD database, including 1,193 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 0.12 (1193 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• 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

ENSG00000285977 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.147 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+2355A>G		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+2355A>G		intron	N/A	ENSP00000489225.1
	ENSG00000285977	ENST00000647648.2		n.361T>C		non_coding_transcript_exon	Exon 3 of 3
	ENSG00000285977	ENST00000837038.1		n.189T>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18137 AN: 152086 Hom.: 1190 Cov.: 32

Gnomad AFR AF: 0.0766

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0899

Gnomad ASJ AF: 0.0936

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.119 AC: 18150 AN: 152204 Hom.: 1193 Cov.: 32 AF XY: 0.117 AC XY: 8683 AN XY: 74418

African (AFR) AF: 0.0765 AC: 3178 AN: 41546

American (AMR) AF: 0.0897 AC: 1372 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0936 AC: 325 AN: 3472

East Asian (EAS) AF: 0.130 AC: 675 AN: 5180

South Asian (SAS) AF: 0.119 AC: 575 AN: 4824

European-Finnish (FIN) AF: 0.141 AC: 1494 AN: 10594

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10158 AN: 67974

Other (OTH) AF: 0.128 AC: 270 AN: 2108

Alfa AF: 0.135 Hom.: 2480

Bravo AF: 0.113

Asia WGS AF: 0.125 AC: 435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.25
DANN	Benign	0.27
PhyloP100		-1.5
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: rs4875371; hg19: chr8-4492509;