8-3408068-C-T

Variant names:

• chr8-3408068-C-T
• rs10088378
• NM_033225.6:c.1902G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4 BP7 BA1

The NM_033225.6(CSMD1):​c.1902G>A​(p.Gln634Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 1,613,398 control chromosomes in the GnomAD database, including 347,504 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 0.66 (33224 hom., cov: 30)
  • Exomes 𝑓: 0.65 (314280 hom.)
• Consequence: CSMD1 NM_033225.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.423
• Publications: 20 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.208).
• BP7: Synonymous conserved (PhyloP=0.423 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.1902G>A	p.Gln634Gln	synonymous_variant	Exon 14 of 70	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.1902G>A	p.Gln634Gln	synonymous_variant	Exon 14 of 69		XP_011533054.1
CSMD1	XM_017013731.2	c.1902G>A	p.Gln634Gln	synonymous_variant	Exon 14 of 64		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.1902G>A	p.Gln634Gln	synonymous_variant	Exon 14 of 70	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99845 AN: 151724 Hom.: 33204 Cov.: 30

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.698

GnomAD2 exomes AF: 0.629 AC: 156658 AN: 248940 AF XY: 0.636

Gnomad AFR exome AF: 0.688

Gnomad AMR exome AF: 0.572

Gnomad ASJ exome AF: 0.657

Gnomad EAS exome AF: 0.371

Gnomad FIN exome AF: 0.648

Gnomad NFE exome AF: 0.666

Gnomad OTH exome AF: 0.654

GnomAD4 exome AF: 0.653 AC: 954941 AN: 1461556 Hom.: 314280 Cov.: 61 AF XY: 0.654 AC XY: 475679 AN XY: 727062

African (AFR) AF: 0.686 AC: 22972 AN: 33474

American (AMR) AF: 0.582 AC: 26006 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 17198 AN: 26136

East Asian (EAS) AF: 0.375 AC: 14879 AN: 39700

South Asian (SAS) AF: 0.657 AC: 56643 AN: 86248

European-Finnish (FIN) AF: 0.650 AC: 34691 AN: 53398

Middle Eastern (MID) AF: 0.759 AC: 4378 AN: 5768

European-Non Finnish (NFE) AF: 0.665 AC: 738784 AN: 1111744

Other (OTH) AF: 0.652 AC: 39390 AN: 60370

GnomAD4 genome AF: 0.658 AC: 99913 AN: 151842 Hom.: 33224 Cov.: 30 AF XY: 0.655 AC XY: 48584 AN XY: 74176

African (AFR) AF: 0.680 AC: 28151 AN: 41420

American (AMR) AF: 0.651 AC: 9936 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2338 AN: 3470

East Asian (EAS) AF: 0.365 AC: 1871 AN: 5128

South Asian (SAS) AF: 0.634 AC: 3044 AN: 4798

European-Finnish (FIN) AF: 0.655 AC: 6888 AN: 10512

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.668 AC: 45371 AN: 67944

Other (OTH) AF: 0.696 AC: 1469 AN: 2112

Alfa AF: 0.660 Hom.: 142098

Bravo AF: 0.657

Asia WGS AF: 0.517 AC: 1797 AN: 3478

EpiCase AF: 0.673

EpiControl AF: 0.685

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	5.0
DANN	Benign	0.40
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs10088378; hg19: chr8-3265590; COSMIC: COSV59298320;