chr8-4554529-A-G

Variant names:

• chr8-4554529-A-G
• rs1526335
• NM_033225.6:c.302+82813T>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.302+82813T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 152,046 control chromosomes in the GnomAD database, including 46,869 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 0.78 (46869 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.302+82813T>C		intron_variant	Intron 2 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.302+82813T>C		intron_variant	Intron 2 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.302+82813T>C		intron_variant	Intron 2 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.302+82813T>C		intron_variant	Intron 2 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118808 AN: 151928 Hom.: 46833 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.865

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.794

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

GnomAD4 genome AF: 0.782 AC: 118901 AN: 152046 Hom.: 46869 Cov.: 32 AF XY: 0.777 AC XY: 57785 AN XY: 74322

African (AFR) AF: 0.708 AC: 29328 AN: 41428

American (AMR) AF: 0.849 AC: 12980 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.865 AC: 3005 AN: 3472

East Asian (EAS) AF: 0.592 AC: 3056 AN: 5160

South Asian (SAS) AF: 0.745 AC: 3593 AN: 4822

European-Finnish (FIN) AF: 0.776 AC: 8193 AN: 10564

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.824 AC: 56061 AN: 68006

Other (OTH) AF: 0.796 AC: 1678 AN: 2108

Alfa AF: 0.810 Hom.: 202268

Bravo AF: 0.784

Asia WGS AF: 0.689 AC: 2398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.9
DANN	Benign	0.38
PhyloP100		0.21
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: rs1526335; hg19: chr8-4412051;