NM_033225.6:c.819-98096A>G

Variant names:

• chr8-3852138-T-C
• rs2930357
• NM_033225.6:c.819-98096A>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.819-98096A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,892 control chromosomes in the GnomAD database, including 10,828 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 0.36 (10828 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 4 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 = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.819-98096A>G		intron_variant	Intron 5 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.819-98096A>G		intron_variant	Intron 5 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.819-98096A>G		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.819-98096A>G		intron_variant	Intron 5 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54087 AN: 151770 Hom.: 10795 Cov.: 32

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.0736

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.357 AC: 54173 AN: 151892 Hom.: 10828 Cov.: 32 AF XY: 0.357 AC XY: 26520 AN XY: 74228

African (AFR) AF: 0.531 AC: 21980 AN: 41400

American (AMR) AF: 0.331 AC: 5046 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1270 AN: 3472

East Asian (EAS) AF: 0.510 AC: 2615 AN: 5128

South Asian (SAS) AF: 0.414 AC: 1992 AN: 4814

European-Finnish (FIN) AF: 0.263 AC: 2786 AN: 10576

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17603 AN: 67934

Other (OTH) AF: 0.350 AC: 738 AN: 2110

Alfa AF: 0.289 Hom.: 11614

Bravo AF: 0.369

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.66
DANN	Benign	0.51
PhyloP100		-1.8
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: rs2930357; hg19: chr8-3709660;