chr8-4360371-C-T

Variant names:

• chr8-4360371-C-T
• rs10104910
• NM_033225.6:c.415+59582G>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.415+59582G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,146 control chromosomes in the GnomAD database, including 2,542 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 0.13 (2542 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033225.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	NM_033225.6	MANE Select	c.415+59582G>A		intron	N/A	NP_150094.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	ENST00000635120.2	TSL:5 MANE Select	c.415+59582G>A		intron	N/A	ENSP00000489225.1
	CSMD1	ENST00000520002.5	TSL:5	c.415+59582G>A		intron	N/A	ENSP00000430733.1
	CSMD1	ENST00000602557.5	TSL:5	c.415+59582G>A		intron	N/A	ENSP00000473359.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20421 AN: 152028 Hom.: 2531 Cov.: 33

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0855

Gnomad ASJ AF: 0.0612

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.0273

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0509

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.134 AC: 20459 AN: 152146 Hom.: 2542 Cov.: 33 AF XY: 0.134 AC XY: 9960 AN XY: 74394

African (AFR) AF: 0.326 AC: 13527 AN: 41464

American (AMR) AF: 0.0854 AC: 1305 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0612 AC: 212 AN: 3466

East Asian (EAS) AF: 0.109 AC: 561 AN: 5164

South Asian (SAS) AF: 0.164 AC: 789 AN: 4818

European-Finnish (FIN) AF: 0.0273 AC: 290 AN: 10604

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0509 AC: 3465 AN: 68024

Other (OTH) AF: 0.130 AC: 275 AN: 2114

Alfa AF: 0.0811 Hom.: 2598

Bravo AF: 0.145

Asia WGS AF: 0.166 AC: 579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.32
DANN	Benign	0.26
PhyloP100		-0.24
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: rs10104910; hg19: chr8-4217893;