rs1540507

Variant names:

• chr8-3231241-C-T
• rs1540507
• NM_033225.6:c.4154-1010G>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.4154-1010G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0871 in 152,170 control chromosomes in the GnomAD database, including 762 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 0.087 (762 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.4154-1010G>A		intron_variant	Intron 26 of 69	ENST00000635120.2	NP_150094.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.4154-1010G>A		intron_variant	Intron 26 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.0871 AC: 13243 AN: 152052 Hom.: 762 Cov.: 33

Gnomad AFR AF: 0.0299

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.0701

Gnomad EAS AF: 0.0531

Gnomad SAS AF: 0.0358

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0753

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

GnomAD4 genome AF: 0.0871 AC: 13261 AN: 152170 Hom.: 762 Cov.: 33 AF XY: 0.0895 AC XY: 6662 AN XY: 74404

African (AFR) AF: 0.0300 AC: 1244 AN: 41518

American (AMR) AF: 0.148 AC: 2261 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0701 AC: 243 AN: 3468

East Asian (EAS) AF: 0.0534 AC: 277 AN: 5186

South Asian (SAS) AF: 0.0365 AC: 176 AN: 4824

European-Finnish (FIN) AF: 0.157 AC: 1663 AN: 10564

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.105 AC: 7145 AN: 68008

Other (OTH) AF: 0.0773 AC: 163 AN: 2108

Alfa AF: 0.0996 Hom.: 1275

Bravo AF: 0.0839

Asia WGS AF: 0.0620 AC: 216 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	0.48
DANN	Benign	0.64
PhyloP100		-0.031
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: rs1540507; hg19: chr8-3088763;