rs10094349

Positions:

• chr8-4332790-T-C
• chr8-4332790-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033225.6(CSMD1):​c.415+87163A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 151,840 control chromosomes in the GnomAD database, including 16,755 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 0.45 (16755 hom., cov: 31)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.383

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD1	NM_033225.6	c.415+87163A>G		intron_variant		ENST00000635120.2
CSMD1	XM_011534752.3	c.415+87163A>G		intron_variant
CSMD1	XM_017013731.2	c.415+87163A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD1	ENST00000635120.2	c.415+87163A>G		intron_variant		5	NM_033225.6	P4

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67805 AN: 151722 Hom.: 16732 Cov.: 31

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.447 AC: 67867 AN: 151840 Hom.: 16755 Cov.: 31 AF XY: 0.450 AC XY: 33402 AN XY: 74184

Gnomad4 AFR AF: 0.666

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.433

Alfa AF: 0.317 Hom.: 1923

Bravo AF: 0.435

Asia WGS AF: 0.438 AC: 1528 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs10094349; hg19: chr8-4190312;