NM_033225.6:c.818+27287G>A

Variant names:

• chr8-3970616-C-T
• rs1529316
• NM_033225.6:c.818+27287G>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.818+27287G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 151,814 control chromosomes in the GnomAD database, including 21,326 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 0.53 (21326 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 16 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.818+27287G>A		intron_variant	Intron 5 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.818+27287G>A		intron_variant	Intron 5 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.818+27287G>A		intron_variant	Intron 5 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.818+27287G>A		intron_variant	Intron 5 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79843 AN: 151696 Hom.: 21311 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.526 AC: 79909 AN: 151814 Hom.: 21326 Cov.: 32 AF XY: 0.535 AC XY: 39660 AN XY: 74176

African (AFR) AF: 0.559 AC: 23154 AN: 41404

American (AMR) AF: 0.536 AC: 8168 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1627 AN: 3464

East Asian (EAS) AF: 0.793 AC: 4097 AN: 5168

South Asian (SAS) AF: 0.624 AC: 3009 AN: 4820

European-Finnish (FIN) AF: 0.561 AC: 5902 AN: 10522

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32267 AN: 67894

Other (OTH) AF: 0.527 AC: 1109 AN: 2104

Alfa AF: 0.493 Hom.: 40976

Bravo AF: 0.524

Asia WGS AF: 0.674 AC: 2343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.044
DANN	Benign	0.75
PhyloP100		-1.2
Mutation Taster		=99/1	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: rs1529316; hg19: chr8-3828138;