NM_033225.6:c.4154-420A>G

Variant names:

• chr8-3230651-T-C
• rs73660619
• NM_033225.6:c.4154-420A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033225.6(CSMD1):​c.4154-420A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 152,196 control chromosomes in the GnomAD database, including 481 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 0.070 (481 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.4154-420A>G		intron_variant	Intron 26 of 69	ENST00000635120.2	NP_150094.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.4154-420A>G		intron_variant	Intron 26 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.0702 AC: 10670 AN: 152080 Hom.: 480 Cov.: 32

Gnomad AFR AF: 0.0774

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.0637

Gnomad ASJ AF: 0.0975

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.0526

Gnomad FIN AF: 0.0472

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0574

Gnomad OTH AF: 0.0721

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

GnomAD4 genome AF: 0.0702 AC: 10679 AN: 152196 Hom.: 481 Cov.: 32 AF XY: 0.0707 AC XY: 5258 AN XY: 74412

African (AFR) AF: 0.0771 AC: 3203 AN: 41524

American (AMR) AF: 0.0641 AC: 980 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0975 AC: 338 AN: 3468

East Asian (EAS) AF: 0.222 AC: 1146 AN: 5158

South Asian (SAS) AF: 0.0526 AC: 254 AN: 4826

European-Finnish (FIN) AF: 0.0472 AC: 501 AN: 10610

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0573 AC: 3900 AN: 68008

Other (OTH) AF: 0.0728 AC: 154 AN: 2116

Alfa AF: 0.0681 Hom.: 753

Bravo AF: 0.0738

Asia WGS AF: 0.117 AC: 410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	9.0
DANN	Benign	0.59
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs73660619; hg19: chr8-3088173;