rs2554622

Positions:

• chr8-3938010-C-A
• chr8-3938010-C-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+59893G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,878 control chromosomes in the GnomAD database, including 11,611 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 0.39 (11611 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.841

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 (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD1	NM_033225.6	c.818+59893G>T		intron_variant		ENST00000635120.2
CSMD1	XM_011534752.3	c.818+59893G>T		intron_variant
CSMD1	XM_017013731.2	c.818+59893G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD1	ENST00000635120.2	c.818+59893G>T		intron_variant		5	NM_033225.6	P4

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58712 AN: 151760 Hom.: 11598 Cov.: 33

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.387 AC: 58766 AN: 151878 Hom.: 11611 Cov.: 33 AF XY: 0.393 AC XY: 29146 AN XY: 74222

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.402

Alfa AF: 0.389 Hom.: 9970

Bravo AF: 0.378

Asia WGS AF: 0.407 AC: 1412 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.44

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: rs2554622; hg19: chr8-3795532;