rs10503267

Positions:

• chr8-4632030-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.302+5312A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,248 control chromosomes in the GnomAD database, including 882 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 0.10 (882 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD1	NM_033225.6	c.302+5312A>G		intron_variant		ENST00000635120.2
CSMD1	XM_011534752.3	c.302+5312A>G		intron_variant
CSMD1	XM_017013731.2	c.302+5312A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD1	ENST00000635120.2	c.302+5312A>G		intron_variant		5	NM_033225.6	P4

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15895 AN: 152130 Hom.: 878 Cov.: 33

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0716

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0992

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.105 AC: 15910 AN: 152248 Hom.: 882 Cov.: 33 AF XY: 0.102 AC XY: 7567 AN XY: 74450

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.0715

Gnomad4 ASJ AF: 0.0637

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.106

Alfa AF: 0.108 Hom.: 453

Bravo AF: 0.102

Asia WGS AF: 0.110 AC: 383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.6
DANN	Benign	0.67

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: rs10503267; hg19: chr8-4489552;