rs2617020

Variant names:

• chr8-4669695-C-T
• rs2617020
• NM_033225.6:c.86-32137G>A

Variant summary

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

The NM_033225.6(CSMD1):​c.86-32137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,952 control chromosomes in the GnomAD database, including 16,374 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 0.46 (16374 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.430
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.86-32137G>A		intron_variant	Intron 1 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.86-32137G>A		intron_variant	Intron 1 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.86-32137G>A		intron_variant	Intron 1 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.86-32137G>A		intron_variant	Intron 1 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69913 AN: 151834 Hom.: 16352 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.497

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

GnomAD4 genome AF: 0.461 AC: 69982 AN: 151952 Hom.: 16374 Cov.: 32 AF XY: 0.460 AC XY: 34192 AN XY: 74252

African (AFR) AF: 0.462 AC: 19141 AN: 41428

American (AMR) AF: 0.574 AC: 8765 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1613 AN: 3468

East Asian (EAS) AF: 0.486 AC: 2505 AN: 5156

South Asian (SAS) AF: 0.540 AC: 2602 AN: 4818

European-Finnish (FIN) AF: 0.375 AC: 3960 AN: 10548

Middle Eastern (MID) AF: 0.517 AC: 151 AN: 292

European-Non Finnish (NFE) AF: 0.437 AC: 29667 AN: 67962

Other (OTH) AF: 0.499 AC: 1051 AN: 2108

Alfa AF: 0.453 Hom.: 28750

Bravo AF: 0.475

Asia WGS AF: 0.540 AC: 1877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.30
DANN	Benign	0.20
PhyloP100		-0.43
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: rs2617020; hg19: chr8-4527217;