rs980238

Variant names:

• chr8-4425096-C-A
• rs980238
• NM_033225.6:c.303-5031G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-4425096-C-A
• chr8-4425096-C-G
• chr8-4425096-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033225.6(CSMD1):​c.303-5031G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 151,672 control chromosomes in the GnomAD database, including 35,177 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 0.68 (35177 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.40
• Publications: 10 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=-1.07).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.303-5031G>T		intron_variant	Intron 2 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.303-5031G>T		intron_variant	Intron 2 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.303-5031G>T		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.303-5031G>T		intron_variant	Intron 2 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.679 AC: 102916 AN: 151554 Hom.: 35160 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.679 AC: 102982 AN: 151672 Hom.: 35177 Cov.: 32 AF XY: 0.673 AC XY: 49906 AN XY: 74102

African (AFR) AF: 0.680 AC: 28147 AN: 41388

American (AMR) AF: 0.659 AC: 10030 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2563 AN: 3466

East Asian (EAS) AF: 0.444 AC: 2282 AN: 5134

South Asian (SAS) AF: 0.611 AC: 2941 AN: 4814

European-Finnish (FIN) AF: 0.673 AC: 7066 AN: 10502

Middle Eastern (MID) AF: 0.752 AC: 218 AN: 290

European-Non Finnish (NFE) AF: 0.703 AC: 47687 AN: 67846

Other (OTH) AF: 0.700 AC: 1474 AN: 2106

Alfa AF: 0.685 Hom.: 29022

Bravo AF: 0.682

Asia WGS AF: 0.567 AC: 1970 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.0050
DANN	Benign	0.22
PhyloP100		-3.4
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: rs980238; hg19: chr8-4282618;