8-3107722-T-C

Variant names:

• chr8-3107722-T-C
• rs3824271
• NM_033225.6:c.6831A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP7 BA1

The NM_033225.6(CSMD1):​c.6831A>G​(p.Glu2277Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 1,571,648 control chromosomes in the GnomAD database, including 515,900 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.80 (48543 hom., cov: 32)
  • Exomes 𝑓: 0.81 (467357 hom.)
• Consequence: CSMD1 NM_033225.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• Publications: 15 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 -9 ACMG points.

• BP7: Synonymous conserved (PhyloP=-0.126 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033225.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	NM_033225.6	MANE Select	c.6831A>G	p.Glu2277Glu	synonymous	Exon 45 of 70	NP_150094.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	ENST00000635120.2	TSL:5 MANE Select	c.6831A>G	p.Glu2277Glu	synonymous	Exon 45 of 70	ENSP00000489225.1	Q96PZ7-1
	CSMD1	ENST00000335551.11	TSL:1	c.5271A>G	p.Glu1757Glu	synonymous	Exon 33 of 56	ENSP00000334828.6	H7BXU2
	CSMD1	ENST00000520002.5	TSL:5	c.6834A>G	p.Glu2278Glu	synonymous	Exon 46 of 71	ENSP00000430733.1	E5RIG2

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121191 AN: 152020 Hom.: 48524 Cov.: 32

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.805

GnomAD2 exomes AF: 0.828 AC: 189612 AN: 228906 AF XY: 0.829

Gnomad AFR exome AF: 0.735

Gnomad AMR exome AF: 0.892

Gnomad ASJ exome AF: 0.829

Gnomad EAS exome AF: 0.958

Gnomad FIN exome AF: 0.799

Gnomad NFE exome AF: 0.798

Gnomad OTH exome AF: 0.822

GnomAD4 exome AF: 0.810 AC: 1149663 AN: 1419510 Hom.: 467357 Cov.: 25 AF XY: 0.812 AC XY: 574889 AN XY: 707834

African (AFR) AF: 0.729 AC: 22876 AN: 31366

American (AMR) AF: 0.886 AC: 35058 AN: 39548

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 21373 AN: 25594

East Asian (EAS) AF: 0.967 AC: 36298 AN: 37540

South Asian (SAS) AF: 0.878 AC: 72424 AN: 82498

European-Finnish (FIN) AF: 0.808 AC: 42928 AN: 53160

Middle Eastern (MID) AF: 0.846 AC: 4805 AN: 5680

European-Non Finnish (NFE) AF: 0.798 AC: 866029 AN: 1085404

Other (OTH) AF: 0.815 AC: 47872 AN: 58720

GnomAD4 genome AF: 0.797 AC: 121263 AN: 152138 Hom.: 48543 Cov.: 32 AF XY: 0.801 AC XY: 59578 AN XY: 74378

African (AFR) AF: 0.742 AC: 30805 AN: 41492

American (AMR) AF: 0.838 AC: 12794 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 2898 AN: 3472

East Asian (EAS) AF: 0.957 AC: 4948 AN: 5172

South Asian (SAS) AF: 0.888 AC: 4281 AN: 4820

European-Finnish (FIN) AF: 0.809 AC: 8556 AN: 10572

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.798 AC: 54277 AN: 68016

Other (OTH) AF: 0.805 AC: 1701 AN: 2112

Alfa AF: 0.800 Hom.: 95561

Bravo AF: 0.797

Asia WGS AF: 0.888 AC: 3088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.1
DANN	Benign	0.47
PhyloP100		-0.13
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3824271; hg19: chr8-2965244; COSMIC: COSV108130700; COSMIC: COSV108130700;