rs6558872

Variant names:

• chr8-4380617-G-A
• rs6558872
• NM_033225.6:c.415+39336C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-4380617-G-A
• chr8-4380617-G-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.415+39336C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,938 control chromosomes in the GnomAD database, including 18,015 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 0.48 (18015 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.581 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.415+39336C>T		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.415+39336C>T		intron	N/A	ENSP00000489225.1	Q96PZ7-1
	CSMD1	ENST00000520002.5	TSL:5	c.415+39336C>T		intron	N/A	ENSP00000430733.1	E5RIG2
	CSMD1	ENST00000602557.5	TSL:5	c.415+39336C>T		intron	N/A	ENSP00000473359.1	E5RIG2

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72817 AN: 151820 Hom.: 17983 Cov.: 32

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.480 AC: 72901 AN: 151938 Hom.: 18015 Cov.: 32 AF XY: 0.482 AC XY: 35750 AN XY: 74224

African (AFR) AF: 0.573 AC: 23734 AN: 41438

American (AMR) AF: 0.557 AC: 8504 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1538 AN: 3468

East Asian (EAS) AF: 0.590 AC: 3041 AN: 5158

South Asian (SAS) AF: 0.599 AC: 2890 AN: 4826

European-Finnish (FIN) AF: 0.343 AC: 3610 AN: 10532

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.414 AC: 28114 AN: 67932

Other (OTH) AF: 0.475 AC: 1002 AN: 2108

Alfa AF: 0.445 Hom.: 49425

Bravo AF: 0.499

Asia WGS AF: 0.617 AC: 2149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.54
DANN	Benign	0.45
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: rs6558872; hg19: chr8-4238139;