8-3640649-T-C

Variant names:

• chr8-3640649-T-C
• rs11136645
• NM_033225.6:c.1010-23852A>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.1010-23852A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 152,056 control chromosomes in the GnomAD database, including 18,738 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 0.49 (18738 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.1010-23852A>G		intron_variant	Intron 7 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.1010-23852A>G		intron_variant	Intron 7 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.1010-23852A>G		intron_variant	Intron 7 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.1010-23852A>G		intron_variant	Intron 7 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74942 AN: 151938 Hom.: 18708 Cov.: 33

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.493 AC: 75020 AN: 152056 Hom.: 18738 Cov.: 33 AF XY: 0.492 AC XY: 36547 AN XY: 74324

African (AFR) AF: 0.547 AC: 22684 AN: 41472

American (AMR) AF: 0.509 AC: 7769 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1868 AN: 3468

East Asian (EAS) AF: 0.518 AC: 2678 AN: 5170

South Asian (SAS) AF: 0.459 AC: 2212 AN: 4820

European-Finnish (FIN) AF: 0.402 AC: 4249 AN: 10576

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31822 AN: 67964

Other (OTH) AF: 0.505 AC: 1067 AN: 2114

Alfa AF: 0.489 Hom.: 36986

Bravo AF: 0.505

Asia WGS AF: 0.471 AC: 1637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.79
DANN	Benign	0.24
PhyloP100		-0.64
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: rs11136645; hg19: chr8-3498171;