rs2623607

Variant names:

• chr8-3687620-T-G
• rs2623607
• NM_033225.6:c.1009+20794A>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.1009+20794A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,112 control chromosomes in the GnomAD database, including 3,215 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 0.19 (3215 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.1009+20794A>C		intron_variant	Intron 7 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.1009+20794A>C		intron_variant	Intron 7 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.1009+20794A>C		intron_variant	Intron 7 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.1009+20794A>C		intron_variant	Intron 7 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28521 AN: 151994 Hom.: 3197 Cov.: 33

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.188 AC: 28595 AN: 152112 Hom.: 3215 Cov.: 33 AF XY: 0.185 AC XY: 13744 AN XY: 74352

African (AFR) AF: 0.321 AC: 13302 AN: 41436

American (AMR) AF: 0.133 AC: 2033 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 686 AN: 3470

East Asian (EAS) AF: 0.142 AC: 734 AN: 5168

South Asian (SAS) AF: 0.141 AC: 679 AN: 4828

European-Finnish (FIN) AF: 0.120 AC: 1267 AN: 10594

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9412 AN: 68002

Other (OTH) AF: 0.191 AC: 403 AN: 2114

Alfa AF: 0.153 Hom.: 1186

Bravo AF: 0.196

Asia WGS AF: 0.164 AC: 569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.086
DANN	Benign	0.68
PhyloP100		-1.3
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: rs2623607; hg19: chr8-3545142;