NM_033225.6:c.1562-22323A>G

Variant names:

• chr8-3431928-T-C
• rs1499693
• NM_033225.6:c.1562-22323A>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.1562-22323A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 152,120 control chromosomes in the GnomAD database, including 37,557 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 0.70 (37557 hom., cov: 34)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.876
• Publications: 0 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.1562-22323A>G		intron_variant	Intron 12 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.1562-22323A>G		intron_variant	Intron 12 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.1562-22323A>G		intron_variant	Intron 12 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.1562-22323A>G		intron_variant	Intron 12 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106422 AN: 152002 Hom.: 37549 Cov.: 34

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.713

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

GnomAD4 genome AF: 0.700 AC: 106472 AN: 152120 Hom.: 37557 Cov.: 34 AF XY: 0.699 AC XY: 51997 AN XY: 74376

African (AFR) AF: 0.611 AC: 25339 AN: 41482

American (AMR) AF: 0.747 AC: 11409 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 2804 AN: 3472

East Asian (EAS) AF: 0.521 AC: 2686 AN: 5158

South Asian (SAS) AF: 0.762 AC: 3678 AN: 4826

European-Finnish (FIN) AF: 0.736 AC: 7787 AN: 10582

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.740 AC: 50336 AN: 68002

Other (OTH) AF: 0.706 AC: 1490 AN: 2110

Alfa AF: 0.726 Hom.: 122569

Bravo AF: 0.696

Asia WGS AF: 0.633 AC: 2198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.30
PhyloP100		-0.88
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: rs1499693; hg19: chr8-3289450;