chr8-3095890-A-G

Variant names:

• chr8-3095890-A-G
• rs7813351
• NM_033225.6:c.7138+959T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033225.6(CSMD1):​c.7138+959T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 152,114 control chromosomes in the GnomAD database, including 14,683 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 0.44 (14683 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.722
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.7138+959T>C		intron_variant	Intron 47 of 69	ENST00000635120.2	NP_150094.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.7138+959T>C		intron_variant	Intron 47 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66397 AN: 151996 Hom.: 14665 Cov.: 33

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.437 AC: 66458 AN: 152114 Hom.: 14683 Cov.: 33 AF XY: 0.446 AC XY: 33145 AN XY: 74356

African (AFR) AF: 0.427 AC: 17731 AN: 41522

American (AMR) AF: 0.432 AC: 6594 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1253 AN: 3468

East Asian (EAS) AF: 0.654 AC: 3376 AN: 5164

South Asian (SAS) AF: 0.545 AC: 2633 AN: 4828

European-Finnish (FIN) AF: 0.522 AC: 5528 AN: 10580

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27882 AN: 67954

Other (OTH) AF: 0.428 AC: 905 AN: 2114

Alfa AF: 0.400 Hom.: 9818

Bravo AF: 0.430

Asia WGS AF: 0.545 AC: 1886 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.060
DANN	Benign	0.56
PhyloP100		-0.72
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: rs7813351; hg19: chr8-2953412;