rs2730048

Variant names:

• chr8-3185790-G-A
• rs2730048
• NM_033225.6:c.5620+2079C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-3185790-G-A
• chr8-3185790-G-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.5620+2079C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,958 control chromosomes in the GnomAD database, including 15,710 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 0.45 (15710 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.5620+2079C>T		intron_variant	Intron 36 of 69	ENST00000635120.2	NP_150094.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.5620+2079C>T		intron_variant	Intron 36 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68673 AN: 151840 Hom.: 15702 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.452 AC: 68720 AN: 151958 Hom.: 15710 Cov.: 32 AF XY: 0.457 AC XY: 33956 AN XY: 74264

African (AFR) AF: 0.494 AC: 20460 AN: 41426

American (AMR) AF: 0.391 AC: 5964 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1810 AN: 3468

East Asian (EAS) AF: 0.540 AC: 2784 AN: 5160

South Asian (SAS) AF: 0.581 AC: 2801 AN: 4822

European-Finnish (FIN) AF: 0.520 AC: 5479 AN: 10542

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27930 AN: 67956

Other (OTH) AF: 0.436 AC: 922 AN: 2114

Alfa AF: 0.405 Hom.: 16633

Bravo AF: 0.441

Asia WGS AF: 0.551 AC: 1914 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.76
PhyloP100		0.059
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: rs2730048; hg19: chr8-3043312;