rs2617019

chr8-4669876-G-Achr8-4669876-G-C

Variant summary

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

The NM_033225.6(CSMD1):c.86-32318C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 151,880 control chromosomes in the GnomAD database, including 20,979 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 0.52 (20979 hom., cov: 31)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD1	NM_033225.6	c.86-32318C>T		intron_variant		ENST00000635120.2
CSMD1	XM_011534752.3	c.86-32318C>T		intron_variant
CSMD1	XM_017013731.2	c.86-32318C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD1	ENST00000635120.2	c.86-32318C>T		intron_variant		5	NM_033225.6	P4

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79272 AN: 151762 Hom.: 20963 Cov.: 31

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.522 AC: 79331 AN: 151880 Hom.: 20979 Cov.: 31 AF XY: 0.522 AC XY: 38754 AN XY: 74236

Gnomad4 AFR AF: 0.478

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.593

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.547

Alfa AF: 0.529 Hom.: 42326

Bravo AF: 0.531

Asia WGS AF: 0.566 AC: 1971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.81
Dann	Benign	0.25

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: rs2617019; hg19: chr8-4527398;