chr8-3826677-C-T

Variant names:

• chr8-3826677-C-T
• rs10088247
• NM_033225.6:c.819-72635G>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.819-72635G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,162 control chromosomes in the GnomAD database, including 43,985 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 0.76 (43985 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472
• Publications: 13 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.819-72635G>A		intron_variant	Intron 5 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.819-72635G>A		intron_variant	Intron 5 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.819-72635G>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.819-72635G>A		intron_variant	Intron 5 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115224 AN: 152044 Hom.: 43943 Cov.: 33

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.823

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.758 AC: 115319 AN: 152162 Hom.: 43985 Cov.: 33 AF XY: 0.756 AC XY: 56227 AN XY: 74380

African (AFR) AF: 0.841 AC: 34916 AN: 41536

American (AMR) AF: 0.753 AC: 11513 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.823 AC: 2859 AN: 3472

East Asian (EAS) AF: 0.800 AC: 4129 AN: 5164

South Asian (SAS) AF: 0.622 AC: 3000 AN: 4820

European-Finnish (FIN) AF: 0.706 AC: 7469 AN: 10572

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.723 AC: 49157 AN: 67994

Other (OTH) AF: 0.750 AC: 1583 AN: 2110

Alfa AF: 0.720 Hom.: 20269

Bravo AF: 0.770

Asia WGS AF: 0.691 AC: 2406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.10
DANN	Benign	0.46
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: rs10088247; hg19: chr8-3684199;