NM_033225.6:c.7661-4702T>A

Variant names:

• chr8-3034215-A-T
• rs1484190
• NM_033225.6:c.7661-4702T>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.7661-4702T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 152,128 control chromosomes in the GnomAD database, including 19,449 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 0.50 (19449 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.566 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.7661-4702T>A		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.7661-4702T>A		intron	N/A	ENSP00000489225.1
	CSMD1	ENST00000335551.11	TSL:1	c.5912-4702T>A		intron	N/A	ENSP00000334828.6
	CSMD1	ENST00000520002.5	TSL:5	c.7664-4702T>A		intron	N/A	ENSP00000430733.1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75863 AN: 152010 Hom.: 19451 Cov.: 33

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.499 AC: 75888 AN: 152128 Hom.: 19449 Cov.: 33 AF XY: 0.496 AC XY: 36910 AN XY: 74362

African (AFR) AF: 0.393 AC: 16310 AN: 41500

American (AMR) AF: 0.504 AC: 7713 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1807 AN: 3468

East Asian (EAS) AF: 0.367 AC: 1901 AN: 5180

South Asian (SAS) AF: 0.398 AC: 1923 AN: 4832

European-Finnish (FIN) AF: 0.551 AC: 5817 AN: 10552

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38787 AN: 67982

Other (OTH) AF: 0.483 AC: 1022 AN: 2114

Alfa AF: 0.390 Hom.: 1018

Bravo AF: 0.492

Asia WGS AF: 0.375 AC: 1305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.3
DANN	Benign	0.75
PhyloP100		-0.47
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: rs1484190; hg19: chr8-2891737;