chr8-4427868-G-C

Variant names:

• chr8-4427868-G-C
• rs1154053
• NM_033225.6:c.303-7803C>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.303-7803C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 152,134 control chromosomes in the GnomAD database, including 54,786 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 0.85 (54786 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.303-7803C>G		intron_variant	Intron 2 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.303-7803C>G		intron_variant	Intron 2 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.303-7803C>G		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.303-7803C>G		intron_variant	Intron 2 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.846 AC: 128617 AN: 152016 Hom.: 54729 Cov.: 32

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.893

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.773

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.860

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

GnomAD4 genome AF: 0.846 AC: 128736 AN: 152134 Hom.: 54786 Cov.: 32 AF XY: 0.844 AC XY: 62794 AN XY: 74358

African (AFR) AF: 0.927 AC: 38489 AN: 41528

American (AMR) AF: 0.819 AC: 12493 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.893 AC: 3097 AN: 3468

East Asian (EAS) AF: 0.731 AC: 3771 AN: 5160

South Asian (SAS) AF: 0.774 AC: 3729 AN: 4816

European-Finnish (FIN) AF: 0.831 AC: 8799 AN: 10588

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.818 AC: 55653 AN: 68002

Other (OTH) AF: 0.861 AC: 1817 AN: 2110

Alfa AF: 0.769 Hom.: 2298

Bravo AF: 0.849

Asia WGS AF: 0.773 AC: 2690 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.43
PhyloP100		-2.2
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: rs1154053; hg19: chr8-4285390;