8-4328228-T-C

Variant names:

• chr8-4328228-T-C
• rs1847570
• NM_033225.6:c.415+91725A>G

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+91725A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 148,608 control chromosomes in the GnomAD database, including 26,248 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 0.59 (26248 hom., cov: 28)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639
• 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

ENSG00000286934 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.415+91725A>G		intron_variant	Intron 3 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.415+91725A>G		intron_variant	Intron 3 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.415+91725A>G		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+91725A>G		intron_variant	Intron 3 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 87293 AN: 148514 Hom.: 26229 Cov.: 28

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.644

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.588 AC: 87349 AN: 148608 Hom.: 26248 Cov.: 28 AF XY: 0.586 AC XY: 42311 AN XY: 72230

African (AFR) AF: 0.460 AC: 18503 AN: 40250

American (AMR) AF: 0.727 AC: 10783 AN: 14834

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2083 AN: 3460

East Asian (EAS) AF: 0.706 AC: 3554 AN: 5034

South Asian (SAS) AF: 0.536 AC: 2521 AN: 4702

European-Finnish (FIN) AF: 0.505 AC: 4800 AN: 9504

Middle Eastern (MID) AF: 0.666 AC: 193 AN: 290

European-Non Finnish (NFE) AF: 0.638 AC: 43109 AN: 67558

Other (OTH) AF: 0.588 AC: 1218 AN: 2070

Alfa AF: 0.604 Hom.: 12888

Bravo AF: 0.602

Asia WGS AF: 0.569 AC: 1971 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.36
PhyloP100		-0.64
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: rs1847570; hg19: chr8-4185750;