chr8-4776893-G-T

Variant names:

• chr8-4776893-G-T
• rs6986423
• NM_033225.6:c.86-139335C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000635120.2(CSMD1):​c.86-139335C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,008 control chromosomes in the GnomAD database, including 21,090 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 0.52 (21090 hom., cov: 33)
• Consequence: CSMD1 ENST00000635120.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• Publications: 5 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 (AMR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000635120.2. 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.86-139335C>A		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.86-139335C>A		intron	N/A	ENSP00000489225.1
	CSMD1	ENST00000520002.5	TSL:5	c.86-139335C>A		intron	N/A	ENSP00000430733.1
	CSMD1	ENST00000602557.5	TSL:5	c.86-139335C>A		intron	N/A	ENSP00000473359.1

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79611 AN: 151890 Hom.: 21066 Cov.: 33

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.524 AC: 79676 AN: 152008 Hom.: 21090 Cov.: 33 AF XY: 0.530 AC XY: 39386 AN XY: 74288

African (AFR) AF: 0.472 AC: 19583 AN: 41450

American (AMR) AF: 0.622 AC: 9503 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1427 AN: 3468

East Asian (EAS) AF: 0.577 AC: 2979 AN: 5162

South Asian (SAS) AF: 0.538 AC: 2591 AN: 4814

European-Finnish (FIN) AF: 0.601 AC: 6346 AN: 10566

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35570 AN: 67962

Other (OTH) AF: 0.525 AC: 1107 AN: 2110

Alfa AF: 0.512 Hom.: 42401

Bravo AF: 0.523

Asia WGS AF: 0.565 AC: 1962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.040
DANN	Benign	0.69
PhyloP100		-1.6
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: rs6986423; hg19: chr8-4634415;