8-3737384-T-C

Variant names:

• chr8-3737384-T-C
• rs2623702
• NM_033225.6:c.931+16546A>G

Variant summary

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

The NM_033225.6(CSMD1):​c.931+16546A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0977 in 152,306 control chromosomes in the GnomAD database, including 895 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 0.098 (895 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238
• Publications: 9 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.931+16546A>G		intron_variant	Intron 6 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.931+16546A>G		intron_variant	Intron 6 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.931+16546A>G		intron_variant	Intron 6 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.931+16546A>G		intron_variant	Intron 6 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.0977 AC: 14866 AN: 152188 Hom.: 897 Cov.: 33

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0646

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0656

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0977 AC: 14875 AN: 152306 Hom.: 895 Cov.: 33 AF XY: 0.0981 AC XY: 7304 AN XY: 74476

African (AFR) AF: 0.139 AC: 5777 AN: 41558

American (AMR) AF: 0.117 AC: 1788 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 254 AN: 3472

East Asian (EAS) AF: 0.189 AC: 980 AN: 5178

South Asian (SAS) AF: 0.117 AC: 563 AN: 4828

European-Finnish (FIN) AF: 0.0646 AC: 686 AN: 10614

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0656 AC: 4463 AN: 68032

Other (OTH) AF: 0.100 AC: 212 AN: 2116

Alfa AF: 0.0757 Hom.: 1675

Bravo AF: 0.106

Asia WGS AF: 0.123 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.4
DANN	Benign	0.70
PhyloP100		-0.24
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: rs2623702; hg19: chr8-3594906;