8-4535412-G-T

Variant names:

• chr8-4535412-G-T
• rs6996668
• NM_033225.6:c.302+101930C>A

Variant summary

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

The NM_033225.6(CSMD1):​c.302+101930C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 151,942 control chromosomes in the GnomAD database, including 3,104 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 0.18 (3104 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.923
• Publications: 2 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

LOC105377789 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.243 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.302+101930C>A		intron	N/A	NP_150094.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	ENST00000635120.2	TSL:5 MANE Select	c.302+101930C>A		intron	N/A	ENSP00000489225.1	Q96PZ7-1
	CSMD1	ENST00000520002.5	TSL:5	c.302+101930C>A		intron	N/A	ENSP00000430733.1	E5RIG2
	CSMD1	ENST00000602557.5	TSL:5	c.302+101930C>A		intron	N/A	ENSP00000473359.1	E5RIG2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28066 AN: 151826 Hom.: 3107 Cov.: 32

Gnomad AFR AF: 0.0650

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.185 AC: 28059 AN: 151942 Hom.: 3104 Cov.: 32 AF XY: 0.186 AC XY: 13794 AN XY: 74202

African (AFR) AF: 0.0649 AC: 2695 AN: 41508

American (AMR) AF: 0.153 AC: 2337 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 750 AN: 3472

East Asian (EAS) AF: 0.220 AC: 1133 AN: 5142

South Asian (SAS) AF: 0.188 AC: 905 AN: 4812

European-Finnish (FIN) AF: 0.274 AC: 2881 AN: 10506

Middle Eastern (MID) AF: 0.190 AC: 55 AN: 290

European-Non Finnish (NFE) AF: 0.246 AC: 16701 AN: 67926

Other (OTH) AF: 0.211 AC: 444 AN: 2108

Alfa AF: 0.181 Hom.: 2353

Bravo AF: 0.170

Asia WGS AF: 0.199 AC: 691 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.27
DANN	Benign	0.31
PhyloP100		-0.92
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: rs6996668; hg19: chr8-4392934;