chr8-4427170-G-A

Variant names:

• chr8-4427170-G-A
• rs4875102
• NM_033225.6:c.303-7105C>T

Variant summary

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

The NM_033225.6(CSMD1):​c.303-7105C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 151,890 control chromosomes in the GnomAD database, including 36,526 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 0.69 (36526 hom., cov: 31)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 9 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.303-7105C>T		intron_variant	Intron 2 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.303-7105C>T		intron_variant	Intron 2 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.303-7105C>T		intron_variant	Intron 2 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.303-7105C>T		intron_variant	Intron 2 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104891 AN: 151772 Hom.: 36514 Cov.: 31

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.768

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.718

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

GnomAD4 genome AF: 0.691 AC: 104946 AN: 151890 Hom.: 36526 Cov.: 31 AF XY: 0.687 AC XY: 50945 AN XY: 74196

African (AFR) AF: 0.651 AC: 26948 AN: 41424

American (AMR) AF: 0.668 AC: 10185 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 2596 AN: 3472

East Asian (EAS) AF: 0.470 AC: 2409 AN: 5130

South Asian (SAS) AF: 0.625 AC: 3008 AN: 4816

European-Finnish (FIN) AF: 0.715 AC: 7542 AN: 10544

Middle Eastern (MID) AF: 0.760 AC: 219 AN: 288

European-Non Finnish (NFE) AF: 0.735 AC: 49908 AN: 67946

Other (OTH) AF: 0.718 AC: 1513 AN: 2106

Alfa AF: 0.708 Hom.: 54682

Bravo AF: 0.687

Asia WGS AF: 0.586 AC: 2042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.48
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: rs4875102; hg19: chr8-4284692;