rs77378271

Variant names:

• chr8-3215967-A-G
• rs77378271
• NM_033225.6:c.4673-1276T>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.4673-1276T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0596 in 150,340 control chromosomes in the GnomAD database, including 345 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 0.060 (345 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• Publications: 12 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 (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.4673-1276T>C		intron_variant	Intron 29 of 69	ENST00000635120.2	NP_150094.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.4673-1276T>C		intron_variant	Intron 29 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.0595 AC: 8949 AN: 150302 Hom.: 343 Cov.: 33

Gnomad AFR AF: 0.0447

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.0498

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0466

Gnomad MID AF: 0.0584

Gnomad NFE AF: 0.0580

Gnomad OTH AF: 0.0639

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

GnomAD4 genome AF: 0.0596 AC: 8954 AN: 150340 Hom.: 345 Cov.: 33 AF XY: 0.0602 AC XY: 4420 AN XY: 73374

African (AFR) AF: 0.0449 AC: 1852 AN: 41266

American (AMR) AF: 0.0499 AC: 751 AN: 15060

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 356 AN: 3468

East Asian (EAS) AF: 0.141 AC: 726 AN: 5144

South Asian (SAS) AF: 0.115 AC: 552 AN: 4794

European-Finnish (FIN) AF: 0.0466 AC: 451 AN: 9686

Middle Eastern (MID) AF: 0.0567 AC: 16 AN: 282

European-Non Finnish (NFE) AF: 0.0579 AC: 3919 AN: 67636

Other (OTH) AF: 0.0649 AC: 136 AN: 2094

Alfa AF: 0.0542 Hom.: 30

Bravo AF: 0.0593

Asia WGS AF: 0.123 AC: 422 AN: 3432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.29
DANN	Benign	0.38
PhyloP100		-0.044
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: rs77378271; hg19: chr8-3073489;