8-4391552-G-C

Variant names:

• chr8-4391552-G-C
• rs11779254
• NM_033225.6:c.415+28401C>G

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+28401C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 151,758 control chromosomes in the GnomAD database, including 25,346 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 0.55 (25346 hom., cov: 30)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73
• Publications: 4 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=-1.07).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.415+28401C>G		intron_variant	Intron 3 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.415+28401C>G		intron_variant	Intron 3 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.415+28401C>G		intron_variant	Intron 3 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.415+28401C>G		intron_variant	Intron 3 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83439 AN: 151640 Hom.: 25301 Cov.: 30

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.550 AC: 83539 AN: 151758 Hom.: 25346 Cov.: 30 AF XY: 0.548 AC XY: 40607 AN XY: 74112

African (AFR) AF: 0.831 AC: 34410 AN: 41396

American (AMR) AF: 0.510 AC: 7760 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1590 AN: 3460

East Asian (EAS) AF: 0.441 AC: 2258 AN: 5122

South Asian (SAS) AF: 0.436 AC: 2101 AN: 4814

European-Finnish (FIN) AF: 0.415 AC: 4360 AN: 10494

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

European-Non Finnish (NFE) AF: 0.432 AC: 29340 AN: 67934

Other (OTH) AF: 0.530 AC: 1117 AN: 2106

Alfa AF: 0.300 Hom.: 660

Bravo AF: 0.568

Asia WGS AF: 0.483 AC: 1681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.15
DANN	Benign	0.32
PhyloP100		-2.7
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: rs11779254; hg19: chr8-4249074;