rs2617019

Variant names:

• chr8-4669876-G-A
• rs2617019
• NM_033225.6:c.86-32318C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-4669876-G-A
• chr8-4669876-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.86-32318C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 151,880 control chromosomes in the GnomAD database, including 20,979 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 0.52 (20979 hom., cov: 31)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403
• Publications: 6 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 = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.86-32318C>T		intron_variant	Intron 1 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.86-32318C>T		intron_variant	Intron 1 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.86-32318C>T		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.86-32318C>T		intron_variant	Intron 1 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79272 AN: 151762 Hom.: 20963 Cov.: 31

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.522 AC: 79331 AN: 151880 Hom.: 20979 Cov.: 31 AF XY: 0.522 AC XY: 38754 AN XY: 74236

African (AFR) AF: 0.478 AC: 19806 AN: 41416

American (AMR) AF: 0.627 AC: 9571 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2053 AN: 3460

East Asian (EAS) AF: 0.489 AC: 2513 AN: 5144

South Asian (SAS) AF: 0.599 AC: 2883 AN: 4812

European-Finnish (FIN) AF: 0.481 AC: 5076 AN: 10550

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35522 AN: 67922

Other (OTH) AF: 0.547 AC: 1154 AN: 2108

Alfa AF: 0.527 Hom.: 91366

Bravo AF: 0.531

Asia WGS AF: 0.566 AC: 1971 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	0.81
DANN	Benign	0.25
PhyloP100		-0.40
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: rs2617019; hg19: chr8-4527398;