rs1442407

Variant names:

• chr8-3234062-G-T
• rs1442407
• NM_033225.6:c.4154-3831C>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.4154-3831C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,028 control chromosomes in the GnomAD database, including 1,996 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 0.15 (1996 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910
• Publications: 11 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.4154-3831C>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.4154-3831C>A		intron_variant	Intron 26 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23335 AN: 151912 Hom.: 1991 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.154 AC: 23360 AN: 152028 Hom.: 1996 Cov.: 32 AF XY: 0.156 AC XY: 11589 AN XY: 74298

African (AFR) AF: 0.104 AC: 4335 AN: 41484

American (AMR) AF: 0.211 AC: 3220 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 588 AN: 3470

East Asian (EAS) AF: 0.239 AC: 1229 AN: 5144

South Asian (SAS) AF: 0.108 AC: 518 AN: 4800

European-Finnish (FIN) AF: 0.186 AC: 1967 AN: 10572

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10897 AN: 67972

Other (OTH) AF: 0.145 AC: 306 AN: 2112

Alfa AF: 0.159 Hom.: 6534

Bravo AF: 0.155

Asia WGS AF: 0.167 AC: 584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.27
PhyloP100		0.091
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: rs1442407; hg19: chr8-3091584;