8-3467279-A-G

Variant names:

• chr8-3467279-A-G
• rs17394506
• NM_033225.6:c.1561+1433T>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.1561+1433T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,200 control chromosomes in the GnomAD database, including 1,519 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 0.14 (1519 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.1561+1433T>C		intron_variant	Intron 12 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.1561+1433T>C		intron_variant	Intron 12 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.1561+1433T>C		intron_variant	Intron 12 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.1561+1433T>C		intron_variant	Intron 12 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21317 AN: 152082 Hom.: 1517 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.140 AC: 21327 AN: 152200 Hom.: 1519 Cov.: 32 AF XY: 0.143 AC XY: 10620 AN XY: 74416

African (AFR) AF: 0.120 AC: 4998 AN: 41530

American (AMR) AF: 0.120 AC: 1840 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 353 AN: 3468

East Asian (EAS) AF: 0.224 AC: 1159 AN: 5174

South Asian (SAS) AF: 0.171 AC: 826 AN: 4828

European-Finnish (FIN) AF: 0.160 AC: 1689 AN: 10582

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10066 AN: 68018

Other (OTH) AF: 0.134 AC: 282 AN: 2110

Alfa AF: 0.145 Hom.: 7305

Bravo AF: 0.136

Asia WGS AF: 0.200 AC: 696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.25
DANN	Benign	0.31
PhyloP100		-0.13
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: rs17394506; hg19: chr8-3324801;