8-3071914-A-G

Variant names:

• chr8-3071914-A-G
• rs7844468
• NM_033225.6:c.7474+15183T>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.7474+15183T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 152,114 control chromosomes in the GnomAD database, including 28,638 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 0.61 (28638 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• Publications: 2 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 (NFE) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033225.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	NM_033225.6	MANE Select	c.7474+15183T>C		intron	N/A	NP_150094.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	ENST00000635120.2	TSL:5 MANE Select	c.7474+15183T>C		intron	N/A	ENSP00000489225.1
	CSMD1	ENST00000335551.11	TSL:1	c.5725+15183T>C		intron	N/A	ENSP00000334828.6
	CSMD1	ENST00000520002.5	TSL:5	c.7477+15183T>C		intron	N/A	ENSP00000430733.1

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92853 AN: 151996 Hom.: 28598 Cov.: 33

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.611 AC: 92938 AN: 152114 Hom.: 28638 Cov.: 33 AF XY: 0.615 AC XY: 45703 AN XY: 74370

African (AFR) AF: 0.606 AC: 25145 AN: 41470

American (AMR) AF: 0.568 AC: 8692 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1878 AN: 3466

East Asian (EAS) AF: 0.463 AC: 2395 AN: 5174

South Asian (SAS) AF: 0.474 AC: 2288 AN: 4824

European-Finnish (FIN) AF: 0.773 AC: 8192 AN: 10596

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42421 AN: 67980

Other (OTH) AF: 0.578 AC: 1222 AN: 2114

Alfa AF: 0.600 Hom.: 19303

Bravo AF: 0.601

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.28
DANN	Benign	0.43
PhyloP100		-2.1
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: rs7844468; hg19: chr8-2929436;