rs10503191

Variant names:

• chr8-3105974-G-C
• rs10503191
• NM_033225.6:c.6949+554C>G

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.6949+554C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 152,302 control chromosomes in the GnomAD database, including 33 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 0.017 (33 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376
• 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=-0.93).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0171 (2608/152302) while in subpopulation EAS AF = 0.0432 (224/5184). AF 95% confidence interval is 0.0386. There are 33 homozygotes in GnomAd4. There are 1249 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 33 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.6949+554C>G		intron_variant	Intron 46 of 69	ENST00000635120.2	NP_150094.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.6949+554C>G		intron_variant	Intron 46 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 2608 AN: 152184 Hom.: 34 Cov.: 32

Gnomad AFR AF: 0.00466

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.0435

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.0146

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0237

Gnomad OTH AF: 0.0158

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

GnomAD4 genome AF: 0.0171 AC: 2608 AN: 152302 Hom.: 33 Cov.: 32 AF XY: 0.0168 AC XY: 1249 AN XY: 74472

African (AFR) AF: 0.00464 AC: 193 AN: 41568

American (AMR) AF: 0.0120 AC: 184 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3470

East Asian (EAS) AF: 0.0432 AC: 224 AN: 5184

South Asian (SAS) AF: 0.0246 AC: 119 AN: 4830

European-Finnish (FIN) AF: 0.0146 AC: 155 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0237 AC: 1609 AN: 68032

Other (OTH) AF: 0.0171 AC: 36 AN: 2110

Alfa AF: 0.0177 Hom.: 3

Bravo AF: 0.0162

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.57
PhyloP100		0.38
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: rs10503191; hg19: chr8-2963496;