rs10503222

Variant names:

• chr8-3916226-C-A
• rs10503222
• NM_033225.6:c.818+81677G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_033225.6(CSMD1):​c.818+81677G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 152,142 control chromosomes in the GnomAD database, including 18 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 0.012 (18 hom., cov: 30)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• 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=-0.82).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0117 (1778/152142) while in subpopulation NFE AF = 0.0177 (1206/68002). AF 95% confidence interval is 0.0169. There are 18 homozygotes in GnomAd4. There are 822 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.818+81677G>T		intron_variant	Intron 5 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.818+81677G>T		intron_variant	Intron 5 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.818+81677G>T		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+81677G>T		intron_variant	Intron 5 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1777 AN: 152024 Hom.: 18 Cov.: 30

Gnomad AFR AF: 0.00476

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00990

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00705

Gnomad FIN AF: 0.00641

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0177

Gnomad OTH AF: 0.00956

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

GnomAD4 genome AF: 0.0117 AC: 1778 AN: 152142 Hom.: 18 Cov.: 30 AF XY: 0.0111 AC XY: 822 AN XY: 74382

African (AFR) AF: 0.00477 AC: 198 AN: 41490

American (AMR) AF: 0.00989 AC: 151 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0271 AC: 94 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5164

South Asian (SAS) AF: 0.00705 AC: 34 AN: 4820

European-Finnish (FIN) AF: 0.00641 AC: 68 AN: 10608

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0177 AC: 1206 AN: 68002

Other (OTH) AF: 0.00946 AC: 20 AN: 2114

Alfa AF: 0.0154 Hom.: 28

Bravo AF: 0.0114

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.36
PhyloP100		-0.055
Mutation Taster		=100/0	polymorphism

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: rs10503222; hg19: chr8-3773748;