8-4046566-C-A

Variant names:

• chr8-4046566-C-A
• rs2740898
• NM_033225.6:c.416-14467G>T

Variant summary

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

The NM_033225.6(CSMD1):​c.416-14467G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 151,902 control chromosomes in the GnomAD database, including 22,796 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 0.54 (22796 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237
• Publications: 0 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.416-14467G>T		intron_variant	Intron 3 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.416-14467G>T		intron_variant	Intron 3 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.416-14467G>T		intron_variant	Intron 3 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.416-14467G>T		intron_variant	Intron 3 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81866 AN: 151782 Hom.: 22787 Cov.: 32

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.539 AC: 81902 AN: 151902 Hom.: 22796 Cov.: 32 AF XY: 0.535 AC XY: 39729 AN XY: 74226

African (AFR) AF: 0.464 AC: 19230 AN: 41438

American (AMR) AF: 0.433 AC: 6587 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2029 AN: 3468

East Asian (EAS) AF: 0.314 AC: 1618 AN: 5154

South Asian (SAS) AF: 0.612 AC: 2939 AN: 4806

European-Finnish (FIN) AF: 0.600 AC: 6320 AN: 10542

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.607 AC: 41240 AN: 67956

Other (OTH) AF: 0.536 AC: 1130 AN: 2108

Alfa AF: 0.591 Hom.: 13750

Bravo AF: 0.517

Asia WGS AF: 0.427 AC: 1487 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.50
PhyloP100		-0.24
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: rs2740898; hg19: chr8-3904088;