rs142816172

Variant names:

• chr8-3298698-C-T
• rs142816172
• NM_033225.6:c.3950+8997G>A

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.3950+8997G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0197 in 152,312 control chromosomes in the GnomAD database, including 41 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 0.020 (41 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639
• Publications: 5 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=-1.02).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0197 (2993/152312) while in subpopulation EAS AF = 0.0318 (165/5182). AF 95% confidence interval is 0.0279. There are 41 homozygotes in GnomAd4. There are 1408 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 41 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.3950+8997G>A		intron_variant	Intron 25 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.3950+8997G>A		intron_variant	Intron 25 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.3950+8997G>A		intron_variant	Intron 25 of 63		XP_016869220.1
CSMD1	XM_011534753.4	c.1043+8997G>A		intron_variant	Intron 8 of 52		XP_011533055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.3950+8997G>A		intron_variant	Intron 25 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2992 AN: 152196 Hom.: 41 Cov.: 33

Gnomad AFR AF: 0.00543

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0182

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.0318

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.0211

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0268

Gnomad OTH AF: 0.0210

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

GnomAD4 genome AF: 0.0197 AC: 2993 AN: 152312 Hom.: 41 Cov.: 33 AF XY: 0.0189 AC XY: 1408 AN XY: 74468

African (AFR) AF: 0.00541 AC: 225 AN: 41570

American (AMR) AF: 0.0182 AC: 278 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 137 AN: 3470

East Asian (EAS) AF: 0.0318 AC: 165 AN: 5182

South Asian (SAS) AF: 0.0151 AC: 73 AN: 4832

European-Finnish (FIN) AF: 0.0211 AC: 224 AN: 10608

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0269 AC: 1827 AN: 68040

Other (OTH) AF: 0.0208 AC: 44 AN: 2114

Alfa AF: 0.0133 Hom.: 4

Bravo AF: 0.0189

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.78
DANN	Benign	0.56
PhyloP100		-0.64
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: rs142816172; hg19: chr8-3156220;