8-4356657-A-G

Variant names:

• chr8-4356657-A-G
• rs10503256
• NM_033225.6:c.415+63296T>C

Variant summary

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

The NM_033225.6(CSMD1):​c.415+63296T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 151,998 control chromosomes in the GnomAD database, including 26,397 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 0.58 (26397 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318
• Publications: 16 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.415+63296T>C		intron_variant	Intron 3 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.415+63296T>C		intron_variant	Intron 3 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.415+63296T>C		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.415+63296T>C		intron_variant	Intron 3 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87718 AN: 151880 Hom.: 26371 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.578 AC: 87794 AN: 151998 Hom.: 26397 Cov.: 32 AF XY: 0.580 AC XY: 43058 AN XY: 74298

African (AFR) AF: 0.396 AC: 16401 AN: 41424

American (AMR) AF: 0.696 AC: 10634 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2226 AN: 3472

East Asian (EAS) AF: 0.640 AC: 3298 AN: 5152

South Asian (SAS) AF: 0.548 AC: 2643 AN: 4822

European-Finnish (FIN) AF: 0.645 AC: 6807 AN: 10560

Middle Eastern (MID) AF: 0.586 AC: 171 AN: 292

European-Non Finnish (NFE) AF: 0.644 AC: 43741 AN: 67966

Other (OTH) AF: 0.594 AC: 1253 AN: 2110

Alfa AF: 0.624 Hom.: 137066

Bravo AF: 0.576

Asia WGS AF: 0.583 AC: 2025 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.32
PhyloP100		0.32
Mutation Taster		=99/1	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: rs10503256; hg19: chr8-4214179;