rs2140340

chr8-3962056-G-Achr8-3962056-G-T

Variant summary

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

The NM_033225.6(CSMD1):c.818+35847C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0842 in 152,218 control chromosomes in the GnomAD database, including 649 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 0.084 (649 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.39

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD1	NM_033225.6	c.818+35847C>T		intron_variant		ENST00000635120.2
CSMD1	XM_011534752.3	c.818+35847C>T		intron_variant
CSMD1	XM_017013731.2	c.818+35847C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD1	ENST00000635120.2	c.818+35847C>T		intron_variant		5	NM_033225.6	P4

Frequencies

GnomAD3 genomes AF: 0.0843 AC: 12819 AN: 152100 Hom.: 650 Cov.: 33

Gnomad AFR AF: 0.0442

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.0876

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0681

Gnomad SAS AF: 0.0899

Gnomad FIN AF: 0.0399

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0980

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

GnomAD4 genome AF: 0.0842 AC: 12823 AN: 152218 Hom.: 649 Cov.: 33 AF XY: 0.0794 AC XY: 5909 AN XY: 74414

Gnomad4 AFR AF: 0.0442

Gnomad4 AMR AF: 0.0877

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.0685

Gnomad4 SAS AF: 0.0899

Gnomad4 FIN AF: 0.0399

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.0965

Alfa AF: 0.103 Hom.: 1195

Bravo AF: 0.0869

Asia WGS AF: 0.0740 AC: 257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.024
Dann	Benign	0.61

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: rs2140340; hg19: chr8-3819578;