rs2140340

Variant names:

• chr8-3962056-G-A
• rs2140340
• NM_033225.6:c.818+35847C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-3962056-G-A
• chr8-3962056-G-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+35847C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0842 in 152,218 control chromosomes in the GnomAD database, including 649 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 0.084 (649 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.39
• Publications: 5 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.818+35847C>T		intron_variant	Intron 5 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.818+35847C>T		intron_variant	Intron 5 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.818+35847C>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+35847C>T		intron_variant	Intron 5 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.0843 AC: 12819 AN: 152100 Hom.: 650 Cov.: 33

Gnomad AFR AF: 0.0442

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.0876

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0681

Gnomad SAS AF: 0.0899

Gnomad FIN AF: 0.0399

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0980

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

GnomAD4 genome AF: 0.0842 AC: 12823 AN: 152218 Hom.: 649 Cov.: 33 AF XY: 0.0794 AC XY: 5909 AN XY: 74414

African (AFR) AF: 0.0442 AC: 1834 AN: 41536

American (AMR) AF: 0.0877 AC: 1341 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 587 AN: 3472

East Asian (EAS) AF: 0.0685 AC: 354 AN: 5170

South Asian (SAS) AF: 0.0899 AC: 433 AN: 4814

European-Finnish (FIN) AF: 0.0399 AC: 423 AN: 10602

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7532 AN: 68012

Other (OTH) AF: 0.0965 AC: 204 AN: 2114

Alfa AF: 0.102 Hom.: 1530

Bravo AF: 0.0869

Asia WGS AF: 0.0740 AC: 257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.024
DANN	Benign	0.61
PhyloP100		-2.4
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: rs2140340; hg19: chr8-3819578;