8-4417435-C-T

Variant names:

• chr8-4417435-C-T
• rs1658815
• NM_033225.6:c.415+2518G>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.415+2518G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 151,824 control chromosomes in the GnomAD database, including 39,853 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 0.71 (39853 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.415+2518G>A		intron_variant	Intron 3 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.415+2518G>A		intron_variant	Intron 3 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.415+2518G>A		intron_variant	Intron 3 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.415+2518G>A		intron_variant	Intron 3 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108064 AN: 151706 Hom.: 39831 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.887

Gnomad FIN AF: 0.804

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.712 AC: 108135 AN: 151824 Hom.: 39853 Cov.: 32 AF XY: 0.716 AC XY: 53128 AN XY: 74170

African (AFR) AF: 0.506 AC: 20972 AN: 41410

American (AMR) AF: 0.710 AC: 10831 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 2918 AN: 3466

East Asian (EAS) AF: 0.937 AC: 4845 AN: 5172

South Asian (SAS) AF: 0.886 AC: 4270 AN: 4822

European-Finnish (FIN) AF: 0.804 AC: 8501 AN: 10570

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.786 AC: 53278 AN: 67816

Other (OTH) AF: 0.748 AC: 1576 AN: 2106

Alfa AF: 0.773 Hom.: 68937

Bravo AF: 0.697

Asia WGS AF: 0.889 AC: 3086 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.57
PhyloP100		-1.9
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: rs1658815; hg19: chr8-4274957;