rs2449222

Positions:

• chr8-3625889-T-C

Variant summary

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

The NM_033225.6(CSMD1):​c.1010-9092A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,164 control chromosomes in the GnomAD database, including 1,277 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 0.11 (1277 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.476

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD1	NM_033225.6	c.1010-9092A>G		intron_variant		ENST00000635120.2
CSMD1	XM_011534752.3	c.1010-9092A>G		intron_variant
CSMD1	XM_017013731.2	c.1010-9092A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD1	ENST00000635120.2	c.1010-9092A>G		intron_variant		5	NM_033225.6	P4

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17259 AN: 152046 Hom.: 1273 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.0749

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0709

Gnomad FIN AF: 0.0651

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0913

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.114 AC: 17289 AN: 152164 Hom.: 1277 Cov.: 32 AF XY: 0.110 AC XY: 8169 AN XY: 74392

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.0747

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0709

Gnomad4 FIN AF: 0.0651

Gnomad4 NFE AF: 0.0913

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0965 Hom.: 367

Bravo AF: 0.118

Asia WGS AF: 0.0460 AC: 161 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.68
DANN	Benign	0.41

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: rs2449222; hg19: chr8-3483411;