8-2938755-C-T

Variant names:

• chr8-2938755-C-T
• rs585000
• NM_033225.6:c.10536-11G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033225.6(CSMD1):​c.10536-11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 1,592,088 control chromosomes in the GnomAD database, including 554,229 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (48688 hom., cov: 32)
  • Exomes 𝑓: 0.84 (505541 hom.)
• Consequence: CSMD1 NM_033225.6 intron
• Scores: Splicing: ADA: 0.0001333
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0350
• Publications: 8 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

LOC105377785 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 8-2938755-C-T is Benign according to our data. Variant chr8-2938755-C-T is described in ClinVar as Benign. ClinVar VariationId is 1276961.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 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.10536-11G>A		intron	N/A	NP_150094.5
	LOC105377785	NR_168441.1		n.1167-62250C>T		intron	N/A
	LOC105377785	NR_168442.1		n.2191+12125C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	ENST00000635120.2	TSL:5 MANE Select	c.10536-11G>A		intron	N/A	ENSP00000489225.1	Q96PZ7-1
	CSMD1	ENST00000335551.11	TSL:1	c.8742-11G>A		intron	N/A	ENSP00000334828.6	H7BXU2
	CSMD1	ENST00000520002.5	TSL:5	c.10539-11G>A		intron	N/A	ENSP00000430733.1	E5RIG2

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121005 AN: 151918 Hom.: 48669 Cov.: 32

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.799

GnomAD2 exomes AF: 0.836 AC: 180981 AN: 216484 AF XY: 0.834

Gnomad AFR exome AF: 0.671

Gnomad AMR exome AF: 0.905

Gnomad ASJ exome AF: 0.865

Gnomad EAS exome AF: 0.900

Gnomad FIN exome AF: 0.829

Gnomad NFE exome AF: 0.825

Gnomad OTH exome AF: 0.828

GnomAD4 exome AF: 0.837 AC: 1205296 AN: 1440052 Hom.: 505541 Cov.: 34 AF XY: 0.838 AC XY: 598211 AN XY: 714140

African (AFR) AF: 0.663 AC: 21984 AN: 33170

American (AMR) AF: 0.899 AC: 37371 AN: 41576

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 22139 AN: 25660

East Asian (EAS) AF: 0.915 AC: 35850 AN: 39168

South Asian (SAS) AF: 0.840 AC: 69846 AN: 83180

European-Finnish (FIN) AF: 0.831 AC: 43499 AN: 52316

Middle Eastern (MID) AF: 0.761 AC: 4352 AN: 5722

European-Non Finnish (NFE) AF: 0.837 AC: 920563 AN: 1099616

Other (OTH) AF: 0.833 AC: 49692 AN: 59644

GnomAD4 genome AF: 0.796 AC: 121075 AN: 152036 Hom.: 48688 Cov.: 32 AF XY: 0.797 AC XY: 59261 AN XY: 74318

African (AFR) AF: 0.678 AC: 28088 AN: 41436

American (AMR) AF: 0.852 AC: 13014 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 2968 AN: 3468

East Asian (EAS) AF: 0.911 AC: 4699 AN: 5160

South Asian (SAS) AF: 0.849 AC: 4094 AN: 4822

European-Finnish (FIN) AF: 0.817 AC: 8624 AN: 10562

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.838 AC: 56998 AN: 67998

Other (OTH) AF: 0.799 AC: 1685 AN: 2108

Alfa AF: 0.819 Hom.: 83700

Bravo AF: 0.794

Asia WGS AF: 0.855 AC: 2974 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.45
DANN	Benign	0.65
PhyloP100		0.035
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00013
dbscSNV1_RF	Benign	0.010
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: rs585000; hg19: chr8-2796277;