8-4786839-C-T

Variant names:

• chr8-4786839-C-T
• rs9314540
• NM_033225.6:c.86-149281G>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.86-149281G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,044 control chromosomes in the GnomAD database, including 1,319 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 0.12 (1319 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240
• Publications: 1 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.86-149281G>A		intron_variant	Intron 1 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.86-149281G>A		intron_variant	Intron 1 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.86-149281G>A		intron_variant	Intron 1 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.86-149281G>A		intron_variant	Intron 1 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18743 AN: 151926 Hom.: 1314 Cov.: 33

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0935

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.123 AC: 18777 AN: 152044 Hom.: 1319 Cov.: 33 AF XY: 0.127 AC XY: 9410 AN XY: 74312

African (AFR) AF: 0.160 AC: 6630 AN: 41458

American (AMR) AF: 0.108 AC: 1647 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0415 AC: 144 AN: 3468

East Asian (EAS) AF: 0.273 AC: 1411 AN: 5160

South Asian (SAS) AF: 0.107 AC: 514 AN: 4824

European-Finnish (FIN) AF: 0.162 AC: 1713 AN: 10546

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0935 AC: 6355 AN: 67988

Other (OTH) AF: 0.125 AC: 265 AN: 2112

Alfa AF: 0.0827 Hom.: 217

Bravo AF: 0.121

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.59
DANN	Benign	0.25
PhyloP100		0.024
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: rs9314540; hg19: chr8-4644361;