rs1350309

Variant names:

• chr8-4755869-G-A
• rs1350309
• NM_033225.6:c.86-118311C>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.86-118311C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 152,082 control chromosomes in the GnomAD database, including 41,048 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 0.73 (41048 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.86-118311C>T		intron_variant	Intron 1 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.86-118311C>T		intron_variant	Intron 1 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.86-118311C>T		intron_variant	Intron 1 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.86-118311C>T		intron_variant	Intron 1 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111405 AN: 151964 Hom.: 41006 Cov.: 33

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.733 AC: 111510 AN: 152082 Hom.: 41048 Cov.: 33 AF XY: 0.736 AC XY: 54666 AN XY: 74324

African (AFR) AF: 0.759 AC: 31511 AN: 41490

American (AMR) AF: 0.783 AC: 11969 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2689 AN: 3468

East Asian (EAS) AF: 0.762 AC: 3923 AN: 5150

South Asian (SAS) AF: 0.750 AC: 3616 AN: 4822

European-Finnish (FIN) AF: 0.725 AC: 7666 AN: 10578

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47757 AN: 67972

Other (OTH) AF: 0.691 AC: 1463 AN: 2116

Alfa AF: 0.710 Hom.: 54515

Bravo AF: 0.736

Asia WGS AF: 0.796 AC: 2772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.86
DANN	Benign	0.56
PhyloP100		-0.60
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: rs1350309; hg19: chr8-4613391;