rs2554622

Variant names:

• chr8-3938010-C-A
• rs2554622
• NM_033225.6:c.818+59893G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-3938010-C-A
• chr8-3938010-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.818+59893G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,878 control chromosomes in the GnomAD database, including 11,611 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 0.39 (11611 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.841
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.818+59893G>T		intron_variant	Intron 5 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.818+59893G>T		intron_variant	Intron 5 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.818+59893G>T		intron_variant	Intron 5 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.818+59893G>T		intron_variant	Intron 5 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58712 AN: 151760 Hom.: 11598 Cov.: 33

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.387 AC: 58766 AN: 151878 Hom.: 11611 Cov.: 33 AF XY: 0.393 AC XY: 29146 AN XY: 74222

African (AFR) AF: 0.313 AC: 12958 AN: 41416

American (AMR) AF: 0.447 AC: 6809 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1229 AN: 3466

East Asian (EAS) AF: 0.472 AC: 2439 AN: 5164

South Asian (SAS) AF: 0.352 AC: 1696 AN: 4824

European-Finnish (FIN) AF: 0.490 AC: 5152 AN: 10518

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27261 AN: 67956

Other (OTH) AF: 0.402 AC: 848 AN: 2108

Alfa AF: 0.384 Hom.: 14183

Bravo AF: 0.378

Asia WGS AF: 0.407 AC: 1412 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.44
PhyloP100		-0.84
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: rs2554622; hg19: chr8-3795532;