rs2163307

Variant names:

• chr8-4448098-C-A
• rs2163307
• NM_033225.6:c.303-28033G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-4448098-C-A
• chr8-4448098-C-G
• chr8-4448098-C-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.303-28033G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,172 control chromosomes in the GnomAD database, including 1,186 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 0.11 (1186 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• 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

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 = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.303-28033G>T		intron_variant	Intron 2 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.303-28033G>T		intron_variant	Intron 2 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.303-28033G>T		intron_variant	Intron 2 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.303-28033G>T		intron_variant	Intron 2 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16574 AN: 152054 Hom.: 1186 Cov.: 33

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.0933

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0896

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.144

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.109 AC: 16580 AN: 152172 Hom.: 1186 Cov.: 33 AF XY: 0.110 AC XY: 8220 AN XY: 74410

African (AFR) AF: 0.0256 AC: 1063 AN: 41552

American (AMR) AF: 0.0932 AC: 1426 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 443 AN: 3464

East Asian (EAS) AF: 0.0898 AC: 465 AN: 5178

South Asian (SAS) AF: 0.221 AC: 1062 AN: 4816

European-Finnish (FIN) AF: 0.153 AC: 1621 AN: 10574

Middle Eastern (MID) AF: 0.141 AC: 41 AN: 290

European-Non Finnish (NFE) AF: 0.147 AC: 10027 AN: 67982

Other (OTH) AF: 0.136 AC: 286 AN: 2108

Alfa AF: 0.127 Hom.: 799

Bravo AF: 0.0968

Asia WGS AF: 0.137 AC: 478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.076
DANN	Benign	0.55
PhyloP100		-1.9
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: rs2163307; hg19: chr8-4305620;