chr8-4338544-A-G

Variant names:

• chr8-4338544-A-G
• rs13267437
• NM_033225.6:c.415+81409T>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.415+81409T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 151,910 control chromosomes in the GnomAD database, including 3,260 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 0.19 (3260 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 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.415+81409T>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.415+81409T>C		intron	N/A	ENSP00000489225.1
	CSMD1	ENST00000520002.5	TSL:5	c.415+81409T>C		intron	N/A	ENSP00000430733.1
	CSMD1	ENST00000602557.5	TSL:5	c.415+81409T>C		intron	N/A	ENSP00000473359.1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29482 AN: 151790 Hom.: 3250 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.00562

Gnomad SAS AF: 0.0793

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.194 AC: 29539 AN: 151910 Hom.: 3260 Cov.: 32 AF XY: 0.193 AC XY: 14328 AN XY: 74204

African (AFR) AF: 0.296 AC: 12267 AN: 41438

American (AMR) AF: 0.183 AC: 2791 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 470 AN: 3470

East Asian (EAS) AF: 0.00563 AC: 29 AN: 5152

South Asian (SAS) AF: 0.0801 AC: 386 AN: 4816

European-Finnish (FIN) AF: 0.176 AC: 1862 AN: 10560

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11085 AN: 67916

Other (OTH) AF: 0.177 AC: 373 AN: 2108

Alfa AF: 0.152 Hom.: 1175

Bravo AF: 0.198

Asia WGS AF: 0.0780 AC: 270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.12
DANN	Benign	0.59
PhyloP100		-0.23
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: rs13267437; hg19: chr8-4196066;