8-2938755-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_033225.6(CSMD1):c.10536-11G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 1,592,088 control chromosomes in the GnomAD database, including 554,229 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.80 (48688 hom., cov: 32)
  • Exomes 𝑓: 0.84 (505541 hom.)
• Consequence: CSMD1 NM_033225.6 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001333
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0350

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]

LOC105377785 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 8-2938755-C-T is Benign according to our data. Variant chr8-2938755-C-T is described in ClinVar as [Benign]. Clinvar id is 1276961.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD1	NM_033225.6	c.10536-11G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000635120.2
LOC105377785	NR_168443.1	n.1172-69813C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD1	ENST00000635120.2	c.10536-11G>A		splice_polypyrimidine_tract_variant, intron_variant		5	NM_033225.6	P4

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121005 AN: 151918 Hom.: 48669 Cov.: 32

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.799

GnomAD3 exomes AF: 0.836 AC: 180981 AN: 216484 Hom.: 76027 AF XY: 0.834 AC XY: 97107 AN XY: 116374

Gnomad AFR exome AF: 0.671

Gnomad AMR exome AF: 0.905

Gnomad ASJ exome AF: 0.865

Gnomad EAS exome AF: 0.900

Gnomad SAS exome AF: 0.837

Gnomad FIN exome AF: 0.829

Gnomad NFE exome AF: 0.825

Gnomad OTH exome AF: 0.828

GnomAD4 exome AF: 0.837 AC: 1205296 AN: 1440052 Hom.: 505541 Cov.: 34 AF XY: 0.838 AC XY: 598211 AN XY: 714140

Gnomad4 AFR exome AF: 0.663

Gnomad4 AMR exome AF: 0.899

Gnomad4 ASJ exome AF: 0.863

Gnomad4 EAS exome AF: 0.915

Gnomad4 SAS exome AF: 0.840

Gnomad4 FIN exome AF: 0.831

Gnomad4 NFE exome AF: 0.837

Gnomad4 OTH exome AF: 0.833

GnomAD4 genome AF: 0.796 AC: 121075 AN: 152036 Hom.: 48688 Cov.: 32 AF XY: 0.797 AC XY: 59261 AN XY: 74318

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.852

Gnomad4 ASJ AF: 0.856

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.817

Gnomad4 NFE AF: 0.838

Gnomad4 OTH AF: 0.799

Alfa AF: 0.810 Hom.: 15850

Bravo AF: 0.794

Asia WGS AF: 0.855 AC: 2974 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.45
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00013
dbscSNV1_RF	Benign	0.010
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: rs585000; hg19: chr8-2796277;