rs13259289

chr8-4252510-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.415+167443A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,132 control chromosomes in the GnomAD database, including 7,862 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 0.29 (7862 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240

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 (NFE) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD1	NM_033225.6	c.415+167443A>G		intron_variant		ENST00000635120.2
CSMD1	XM_011534752.3	c.415+167443A>G		intron_variant
CSMD1	XM_017013731.2	c.415+167443A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD1	ENST00000635120.2	c.415+167443A>G		intron_variant		5	NM_033225.6	P4

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44137 AN: 152014 Hom.: 7865 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.00482

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.290 AC: 44140 AN: 152132 Hom.: 7862 Cov.: 33 AF XY: 0.287 AC XY: 21315 AN XY: 74378

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.00502

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.294

Alfa AF: 0.373 Hom.: 14634

Bravo AF: 0.279

Asia WGS AF: 0.0830 AC: 287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.80
Dann	Benign	0.77

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: rs13259289; hg19: chr8-4110032;