NM_033225.6:c.1448+5049T>C

Variant names:

• chr8-3488574-A-G
• rs17066250
• NM_033225.6:c.1448+5049T>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.1448+5049T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,236 control chromosomes in the GnomAD database, including 1,570 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 (1570 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 0 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.1448+5049T>C		intron_variant	Intron 11 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.1448+5049T>C		intron_variant	Intron 11 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.1448+5049T>C		intron_variant	Intron 11 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.1448+5049T>C		intron_variant	Intron 11 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21118 AN: 152116 Hom.: 1564 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0957

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0927

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.139 AC: 21154 AN: 152236 Hom.: 1570 Cov.: 32 AF XY: 0.140 AC XY: 10394 AN XY: 74432

African (AFR) AF: 0.182 AC: 7557 AN: 41530

American (AMR) AF: 0.149 AC: 2279 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0957 AC: 332 AN: 3470

East Asian (EAS) AF: 0.231 AC: 1196 AN: 5184

South Asian (SAS) AF: 0.149 AC: 721 AN: 4826

European-Finnish (FIN) AF: 0.0927 AC: 983 AN: 10602

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7751 AN: 68008

Other (OTH) AF: 0.122 AC: 258 AN: 2116

Alfa AF: 0.122 Hom.: 3416

Bravo AF: 0.144

Asia WGS AF: 0.204 AC: 709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.35
DANN	Benign	0.24
PhyloP100		-1.1
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: rs17066250; hg19: chr8-3346096;