NM_033225.6:c.1009+1739G>T

Variant names:

• chr8-3706675-C-A
• rs17326670
• NM_033225.6:c.1009+1739G>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.1009+1739G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,746 control chromosomes in the GnomAD database, including 11,425 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 0.38 (11425 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033225.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	NM_033225.6	MANE Select	c.1009+1739G>T		intron	N/A	NP_150094.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	ENST00000635120.2	TSL:5 MANE Select	c.1009+1739G>T		intron	N/A	ENSP00000489225.1
	CSMD1	ENST00000520002.5	TSL:5	c.1009+1739G>T		intron	N/A	ENSP00000430733.1
	CSMD1	ENST00000602557.5	TSL:5	c.1009+1739G>T		intron	N/A	ENSP00000473359.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57882 AN: 151630 Hom.: 11430 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.382 AC: 57895 AN: 151746 Hom.: 11425 Cov.: 32 AF XY: 0.385 AC XY: 28523 AN XY: 74166

African (AFR) AF: 0.286 AC: 11806 AN: 41322

American (AMR) AF: 0.369 AC: 5630 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1602 AN: 3464

East Asian (EAS) AF: 0.554 AC: 2849 AN: 5146

South Asian (SAS) AF: 0.481 AC: 2315 AN: 4812

European-Finnish (FIN) AF: 0.401 AC: 4225 AN: 10534

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28178 AN: 67890

Other (OTH) AF: 0.385 AC: 811 AN: 2108

Alfa AF: 0.410 Hom.: 6611

Bravo AF: 0.377

Asia WGS AF: 0.457 AC: 1584 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.45
PhyloP100		-0.24
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: rs17326670; hg19: chr8-3564197;